Science.gov

Sample records for 2-year carcinogenicity studies

  1. Low-Dose Carcinogenicity Studies

    EPA Science Inventory

    One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

  2. Critical analysis of carcinogenicity study outcomes. Relationship with pharmacological properties.

    PubMed

    van der Laan, Jan Willem; Kasper, Peter; Silva Lima, Beatriz; Jones, David R; Pasanen, Markku

    2016-08-01

    Predicting the outcome of life-time carcinogenicity studies in rats based on chronic (6-month) toxicity studies in this species is possible in some instances. This should reduce the number of such studies and hence have a significant impact on the total number of animals used in safety assessment of new medicines. From a regulatory perspective, this should be sufficient to grant a waiver for a carcinogenicity study in those cases where there is confidence in the outcome of the prediction. Pharmacological properties are a frequent key factor for the carcinogenic mode of action of some pharmaceuticals, but data-analysis on a large dataset has never been formally conducted. We have conducted an analysis of a dataset based on the perspective of the pharmacology of 255 compounds from industrial and regulatory sources. It is proposed that a pharmacological, class-specific, model may consist of an overall causal relationship between the pharmacological class and the histopathology findings in rats after 6 months treatment, leading to carcinogenicity outcome after 2 years. Knowledge of the intended drug target and pathway pharmacology should enhance the prediction of either positive or negative outcomes of rat carcinogenicity studies. The goal of this analysis is to review the pharmacological properties of compounds together with the histopathology findings from the chronic toxicity study in rodents in order to introduce an integrated approach to estimate the risk of human carcinogenicity of pharmaceuticals. This approach would allow scientists to define conditions under which 2-year rat carcinogenicity studies will or will not add value to such an assessment. We have demonstrated the possibility of a regulatory waiver for a carcinogenicity study in rats, as currently discussed in the International Council for Harmonization (ICH) - formerly known as the International Conference on Harmonization (ICH), by applying the proposed prediction approach in a number of case studies

  3. Comparative results of 327 chemical carcinogenicity studies.

    PubMed Central

    Haseman, J K; Huff, J E; Zeiger, E; McConnell, E E

    1987-01-01

    The National Cancer Institute (NCI) and the National Toxicology Program (NTP) have carried out a number of laboratory animal carcinogenicity studies and presented the results of these experiments in a series of Technical Reports. This paper tabulates the results of the 327 NCI/NTP studies carried out to date on 308 distinct chemicals, and discusses certain issues relevant to the evaluation of carcinogenicity in these experiments. This compilation of results from NCI/NTP carcinogenicity experiments provides a large database that can be used to study structure-activity correlations, interspecies concordance, and associations between laboratory animal carcinogenicity and other toxicological effects. PMID:3691430

  4. Carcinogenicity of acrylamide in B6C3F(1) mice and F344/N rats from a 2-year drinking water exposure.

    PubMed

    Beland, Frederick A; Mellick, Paul W; Olson, Greg R; Mendoza, Maria C B; Marques, M Matilde; Doerge, Daniel R

    2013-01-01

    Acrylamide is a component of roasted coffee and certain baked and fried carbohydrate-rich foods prepared at high temperatures. We have assessed the carcinogenicity of acrylamide in male and female B6C3F(1) mice and F344/N rats administered 0, 0.0875, 0.175, 0.35, or 0.70mM acrylamide in the drinking water ad libitum for 2 years. Acrylamide caused significant dose-related decreasing trends in the body weights of F344/N rats. Acrylamide administration resulted in significant dose-related decreasing trends in survival in both sexes of B6C3F(1) mice and in female F344/N rats. Histopathological analyses indicated significant dose-related increases in Harderian gland and lung tumors in male and female B6C3F(1) mice. Male B6C3F(1) mice also had a significantly increased incidence of forestomach tumors, while female B6C3F(1) mice had significant dose-related increases in mammary gland, ovary, and skin tumors. In male and female F344/N rats, there were significant increases in thyroid tumors. Male F344/N rats also had significant dose-related increases in testes, heart, and pancreas tumors, while female F344 rats demonstrated significant increases in clitoral gland, mammary gland, oral cavity, and skin tumors. These results, combined with previous mechanistic studies, provide strong support for the concept that acrylamide is activated to a carcinogen through metabolism to glycidamide. PMID:23009883

  5. Study of Chemical Carcinogens by Positron Annihilation Lifetime Spectroscopy

    NASA Astrophysics Data System (ADS)

    Pivtsaev, A. A.; Razov, V. I.; Karasev, A. O.

    2013-11-01

    We have used positron annihilation lifetime spectroscopy to study the carcinogens C21H20BrN3, C4H7Cl2O4P, CCl4, CHCl3, AlF3, C8H12N4O, C6H4Cl2 and the non-carcinogens H2O, AlCl3, CH2Cl2, C2H6OS. We have established a correlation between the annihilation characteristics of the studied compounds and their degree of carcinogenicity.

  6. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure.

    PubMed

    Stout, Matthew D; Herbert, Ronald A; Kissling, Grace E; Suarez, Fernando; Roycroft, Joseph H; Chhabra, Rajendra S; Bucher, John R

    2008-02-28

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800ppm by inhalation, 6h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800ppm. Body weight gains were decreased in male rats at 900 and 1800ppm and in female mice at 1800ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through alpha2micro-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800ppm, indicating that CPN was increased by mechanisms in addition to those related to alpha2micro-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800ppm. The

  7. Issues in the Design and Interpretation of Chronic Toxicity and Carcinogenicity Studies in Rodents: Approaches to Dose Selection

    EPA Science Inventory

    For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has ...

  8. Lifetime carcinogenicity study of 1- and 2-naphthylamine in dogs.

    PubMed Central

    Purchase, I. F.; Kalinowski, A. E.; Ishmael, J.; Wilson, J.; Gore, C. W.; Chart, I. S.

    1981-01-01

    Groups of male and female beagle dogs were given daily doses of 400 mg of various mixtures of naphthylamines for up to 109 months. Survivors were killed at 128 months. A variety of pathological conditions was diagnosed, but the only effect related to treatment was the induction of bladder neoplasms. All dogs which received pure 2-naphthylamine developed transitional-cell carcinomas of the bladder within 34 months. Two of 8 dogs receiving 6% 2-naphthylamine in 1-naphthylamine developed early carcinoma and 2/8 dogs receiving 0.5% 2-naphthylamine in 1-naphthylamine developed haemangioma of the bladder. Some of the dogs receiving 1-naphthylamine (total dose 950 g) and the controls had focal cystitis or hyperplasia, but no neoplasia of the bladder. These results confirm the carcinogenicity of 2-naphthylamine to dogs. No carcinogenic effect of 1-naphthylamine was observed, indicating that it is at least 200 times less potent as a carcinogen than 2-naphthylamine. The incidence of bladder cancer in dogs fed mixtures of both naphthylamines explains why previous experimental and epidemiological studies of impure 1-naphthylamine have revealed carcinogenicity. Images Fig. 1 Fig. 2 PMID:7326199

  9. Conflicting Views on Chemical Carcinogenesis Arising from the Design and Evaluation of Rodent Carcinogenicity Studies

    PubMed Central

    Melnick, Ronald L.; Thayer, Kristina A.; Bucher, John R.

    2008-01-01

    Conflicting views have been expressed frequently on assessments of human cancer risk of environmental agents based on animal carcinogenicity data; this is primarily because of uncertainties associated with extrapolations of toxicologic findings from studies in experimental animals to human circumstances. Underlying these uncertainties are issues related to how experiments are designed, how rigorously hypotheses are tested, and to what extent assertions extend beyond actual findings. National and international health agencies regard carcinogenicity findings in well-conducted experimental animal studies as evidence of potential carcinogenic risk to humans. Controversies arise when both positive and negative carcinogenicity data exist for a specific agent or when incomplete mechanistic data suggest a possible species difference in response. Issues of experimental design and evaluation that might contribute to disparate results are addressed in this article. To serve as reliable sources of data for the evaluation of the carcinogenic potential of environmental agents, experimental studies must include a) animal models that are sensitive to the end points under investigation; b) detailed characterization of the agent and the administered doses; c) challenging doses and durations of exposure (at least 2 years for rats and mice); d) sufficient numbers of animals per dose group to be capable of detecting a true effect; e) multiple dose groups to allow characterization of dose–response relationships, f) complete and peer-reviewed histopathologic evaluations; and g) pairwise comparisons and analyses of trends based on survival-adjusted tumor incidence. Pharmacokinetic models and mechanistic hypotheses may provide insights into the biological behavior of the agent; however, they must be adequately tested before being used to evaluate human cancer risk. PMID:18197312

  10. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    PubMed

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

  11. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies

    PubMed Central

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-01-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

  12. Perinatal Toxicity and Carcinogenicity Studies of Styrene –Acrylonitrile Trimer, A Ground Water Contaminant

    PubMed Central

    Behl, Mamta; Elmore, Susan A.; Malarkey, David E.; Hejtmancik, Milton R.; Gerken, Diane K.; Chhabra, Rajendra S.

    2015-01-01

    Styrene Acrylonitrile (SAN) Trimer is a by-product in the production of acrylonitrile styrene plastics. Following a report of a childhood cancer cluster in the Toms River section of Dover Township, New Jersey, SAN Trimer was identified as one of the groundwater contaminants at Reich Farm Superfund site in the township. The contaminants from the Reich Farm site’s ground water plume impacted two wells at the Parkway well field. The National Toxicology Program (NTP) studied the toxicity and carcinogenicity of SAN Trimer in rats exposed during their perinatal developmental period and adulthood. The chronic toxicity and carcinogenicity studies in F344/N rats were preceded by 7- and 18-week perinatal toxicity studies to determine the exposure concentrations for the 2-year studies. Subsequently, Fisher 344 pregnant dams were exposed to SAN Trimer containing diet at 400, 800, or 1600 ppm concentrations during gestation, nursing and weaning periods of offspring followed by two year of adult exposures to both male and female pups. There was no statistically significant evidence of carcinogenic activity following SAN-Trimer exposure; however, rare neoplasms in the brain and spinal cord were observed in males and to lesser extent in female rats. These incidences were considered within the range of historical background in the animal model used in the current studies. Therefore, the presence of a few rarely occurring CNS tumors in the treated groups were not judged to be associated with the SAN Trimer exposure. The major finding was a dose-related peripheral neuropathy associated with the sciatic nerves in females and spinal nerve roots in males and females thereby suggesting that SAN trimer is potentially a nervous system toxicant. PMID:24060431

  13. LARGE SCALE CARCINOGEN DOSE RESPONSE STUDIES WITH JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    To investigate the responses to low carcinogen doses in animal models, large sample sizes are needed and it is an advantage if the model has a low spontaneous tumor rate. Three large scale dose response studies were conducted using Japanese medaka and the carcinogen diethylnitros...

  14. Toxicity and carcinogenicity studies of Ginkgo biloba extract in rat and mouse: liver, thyroid, and nose are targets.

    PubMed

    Rider, Cynthia V; Nyska, Abraham; Cora, Michelle C; Kissling, Grace E; Smith, Cynthia; Travlos, Gregory S; Hejtmancik, Milton R; Fomby, Laurene M; Colleton, Curtis A; Ryan, Michael J; Kooistra, Linda; Morrison, James P; Chan, Po C

    2014-07-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, 3-month and 2-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program's Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use. PMID:23960164

  15. Many Kidney Transplant Patients Land in ER Within 2 Years: Study

    MedlinePlus

    ... news/fullstory_157959.html Many Kidney Transplant Patients Land in ER Within 2 Years: Study Findings show need to coordinate care after organ transplant, researcher says To use the sharing features on this page, please enable ...

  16. A carcinogenicity study of sucralose in the CD-1 mouse.

    PubMed

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The potential carcinogenicity of sucralose was evaluated by feeding groups of 52 male and 52 female CD-1 mice a diet containing sucralose at 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) for 104 weeks. A group of 72 male and 72 female mice received diet without sucralose and served as controls. Week 1 achieved doses ranging from 543 to 5870mg/kg body weight/day in the low-dose males and high-dose females, respectively. Sucralose had no adverse effect on survival. No significant changes attributable to sucralose were found in the clinical condition or behaviour of the mice. Organ weights and the gross appearance of tissues were unaffected by treatment. The mean erythrocyte counts of females receiving the highest dietary concentration were slightly, but statistically significantly, lower than those of the controls after 104 weeks of treatment. Group mean body weight gain at the highest dietary concentration of sucralose was significantly less than that of the control in mice of both sexes. Food consumption, after correction for sucralose content, was lower for female mice, but not statistically significant. Water consumption for male mice receiving the highest dietary concentration was approximately 9% higher than that of the controls. There were statistically significant increases in the incidence of several non-neoplastic findings, but these were not considered to be related to sucralose administration. Treatment with sucralose did not increase the incidence of any tumour or influence the types of tumours observed. It was concluded that sucralose is not carcinogenic in CD-1 mice. The body weight gain and erythrocyte observations at the 3.0% dietary level were of limited biological significance as they were not accompanied by any histopathologic finding and had no impact on survival. The remaining dose levels were judged to have no effects. PMID:10882820

  17. Injection-site malignant fibrous histiocytomas in a pegvisomant carcinogenicity study in SD rats.

    PubMed

    Bartholomew, Phillip M; Kreeger, John M; Morton, Daniel

    2014-10-01

    In a 2-year rat carcinogenicity study, pegvisomant injected subcutaneously on a daily basis at doses of 0, 2, 8, or 20 mg/kg/day produced malignant fibrous histiocytomas (MFHs) at the injection sites of 3 male rats (5%) given 8 mg/kg/day and 5 males (8%) given 20 mg/kg/day. MFH was characterized by unencapsulated dermal and subcutaneous sheets of fusiform and spindle-shaped cells sometimes with areas of round and/or irregular, pleomorphic cells and variable numbers of large multinucleated giant cells. Some regions of MFH had a fibroblastic appearance with streaming cells forming storiform patterns, while other areas consisted primarily of round to plump irregular cells with more giant cells. Pegvisomant did not increase the incidence of MFH in female rats and did not produce any other neoplastic responses in rats. In the dermis and subcutis at the injection sites of many males and females, pegvisomant produced dose-related increased incidences and severity of histiocytic infiltrates consisting of vacuolated macrophages with variable mature or immature fibrous tissue. Neoplasms at injection sites did not result in marketing restrictions or a label warning for human cancer risk, highlighting that injection-site neoplasms in rats have low relevance for human risk assessment. PMID:24487355

  18. Improving Social Competence through Emotion Knowledge in 2-Year-Old Children: A Pilot Study

    ERIC Educational Resources Information Center

    Giménez-Dasí, Marta; Fernández-Sánchez, Marta; Quintanilla, Laura

    2015-01-01

    Research Findings: The goal of this study was to determine the efficacy of an educational intervention program to improve emotion knowledge, emotion regulation, and social competence in 2-year-old Spanish children. This study makes two original contributions because there are no validated education programs for such young children and because it…

  19. Carcinogens in Israeli milk: a study in regulatory failure.

    PubMed

    Westin, J B

    1993-01-01

    The potential danger to humans of exposure to chemicals shown to be carcinogenic in animals has become increasingly clear in the last 20 years. A gap still exists, however, between the appreciation of the risk by scientists and the willingness of public health authorities to reduce it. Three pesticides, shown repeatedly to produce over a dozen different types of cancer in rats and mice, were discovered in inordinately high concentrations in Israeli milk and dairy products. The three pesticides--alpha-BHC, gamma-BHC (lindane), and DDT--had been shown to be present for ten years or more at mean concentrations up to 100 times those found in U.S. dairy products--with resultant concentrations in breast milk being possibly 800 times greater than those in the United States--yet neither the Ministry of Health nor the Israel Cancer Association made any apparent moves either to warn the public or to rectify the situation. A small consumer organization, Consumer Shield, brought the issue into the open. Through public pressure, court action, and the threat of further legal redress--and despite repeated attacks in the media by the milk producers, the Ministry, and the Cancer Association--Consumer Shield forced the authorities to outlaw the use of alpha-BHC and lindane (DDT no longer being in general use). The ban resulted in a precipitous drop in the concentrations of these substances in Israeli milk. Recent epidemiological and laboratory findings suggest that the dramatic drop in breast cancer mortality rates subsequent to the pesticide ban could be a direct result of that ban. PMID:8375952

  20. A feasibility study: Can information collected to classify for mutagenicity be informative in predicting carcinogenicity?

    PubMed

    Petkov, Petko I; Patlewicz, Grace; Schultz, Terry W; Honma, Masamitsu; Todorov, Milen; Kotov, Stefan; Dimitrov, Sabcho D; Donner, E Maria; Mekenyan, Ovanes G

    2015-06-01

    Carcinogenicity is a complex endpoint of high concern yet the rodent bioassay still used is costly to run in terms of time, money and animals. Therefore carcinogenicity has been the subject of many different efforts to both develop short-term tests and non-testing approaches capable of predicting genotoxic carcinogenic potential. In our previous publication (Mekenyan et al., 2012) we presented an in vitro-in vivo extrapolation workflow to help investigate the differences between in vitro and in vivo genotoxicity tests. The outcomes facilitated the development of new (Q)SAR models and for directing testing. Here we have refined this workflow by grouping specific tests together on the basis of their ability to detect DNA and/or protein damage at different levels of biological organization. This revised workflow, akin to an Integrated Approach to Testing and Assessment (IATA) informed by mechanistic understanding was helpful in rationalizing inconsistent study outcomes and categorizing a test set of carcinogens with mutagenicity data on the basis of regulatory mutagenicity classifications. Rodent genotoxic carcinogens were found to be correctly predicted with a high sensitivity (90-100%) and a low rate of false positives (3-10%). The insights derived are useful to consider when developing future (non-)testing approaches to address regulatory purposes. PMID:25792138

  1. Genetic, kinetic, and mechanistic studies on the inhibition of interferon production by polycyclic aromatic hydrocarbon carcinogens

    SciTech Connect

    Golemboski, K.A.L.

    1984-01-01

    Interferon (IFN) production is inhibited by treatment with chemical carcinogens. The significance of this inhibition is not clear. The interaction of IFN with cytochrome P-450 and associated enzymes, which are responsible for the metabolism and/or activation of many carcinogens, and with the immune system suggests that the developement of a cancer could be influenced by this inhibition. The effect of 7,12-dimethylbenz(a)anthracene (DMBA) on IFN-..gamma.. production in murine spleen cell cultures was inhibited when DMBA was given 24 hours before or 4-5 hours after IFN-..gamma.. was induced with phytohemagglutinin-p (PHA-P). The influence of genetic controls of IFN inhibition was examined using DBA/2, C57B1/6, ICR, and SENCAR mouse strains. Kinetic studies examined parameters of IFN inhibition by benzo(a)pyrene (BP). IFN production in treated cells equaled that of untreated cells, but was delayed by six to twelve hours, suggesting a reversible inhibition. The approximate decrease in cell number which would be required to decrease IFN significantly was determined to be 50%. These results indicated that production of all types of IFN is inhibited by carcinogen treatment and that the inhibition may be genetically controlled. The inhibition of IFN production is actually a rapidly reversible delay. Exposure to the carcinogen is required only for uptake, and extended exposure, or another carcinogen, can interfere with the inhibition of IFN production by subsequent doses.

  2. Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se.

    PubMed

    Haussmann, Hans-Juergen; Fariss, Marc W

    2016-09-01

    The effects of long-term use of nicotine per se on cancer risk, in the absence of tobacco extract or smoke, are not clearly understood. This review evaluates the strength of published scientific evidence, in both epidemiological and animal studies, for the potential carcinogenic effects of nicotine per se; that is to act as a complete carcinogen or as a modulator of carcinogenesis. For human studies, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a carcinogenic effect due to the limited information available. In animal studies, limited evidence suggests an association between long-term nicotine exposure and a lack of a complete carcinogenic effect. Conclusive studies using current bioassay guidelines, however, are missing. In studies using chemical/physical carcinogens or transgenic models, there appears to be inadequate evidence for an association between nicotine exposure and the presence of or lack of a modulating (stimulating) effect on carcinogenesis. This is primarily due to the large number of conflicting studies. In contrast, a majority of studies provides sufficient evidence for an association between nicotine exposure and enhanced carcinogenesis of cancer cells inoculated in mice. This modulating effect was especially prominent in immunocompromized mice. Overall, taking the human and animal studies into consideration, there appears to be inadequate evidence to conclude that nicotine per se does or does not cause or modulate carcinogenesis in humans. This conclusion is in agreement with the recent US Surgeon General's 2014 report on the health consequences of nicotine exposure. PMID:27278157

  3. Natrelle 410 Extra-Full Projection Silicone Breast Implants: 2-Year Results from Two Prospective Studies

    PubMed Central

    McGuire, Patricia; Murphy, Diane K.

    2015-01-01

    Background: The safety and effectiveness of the Natrelle Style 410 highly cohesive silicone gel breast implant (Allergan, Inc., Irvine, Calif.) in full or moderate height and projection have been shown in a 10-year study. Extra-full projection implants may be an appropriate option for some women undergoing breast reconstruction. Methods: A total of 2795 women received at least one Natrelle 410 extra-full projection implant (X-style) for breast reconstruction in two similarly designed, prospective, multicenter studies. Data collected for 2 years after implantation in these studies were pooled to evaluate complication rates and subject and physician satisfaction. Results: Most subjects (76.0 percent) underwent bilateral reconstruction; a total of 4912 devices were implanted. Complication rates at 2 years were low. The most common complications were asymmetry (4.8 percent) and capsular contracture (3.3 percent). The cumulative risk of reoperation was 21.6 percent by subject and 16.6 percent by device; the most common reasons for reoperation were scarring (n = 97), asymmetry (n = 89), implant malposition (n = 78), and infection (n = 71). Subject and physician satisfaction rates exceeded 90 percent. At 2 years, 97 percent of physicians reported that the shape of the breast reflected the shape of the implant, and that the breast implant had maintained its original position. Conclusions: The safety profile of the Natrelle 410 extra-full projection implant mirrors that of its moderate projection and full projection counterparts. Both physicians and subjects were highly satisfied with the implants 2 years after surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV. PMID:26090764

  4. Comment on the significance of positive carcinogenicity studies using gavage as the route of exposure.

    PubMed Central

    Perera, F; Brennan, T; Fouts, J R

    1989-01-01

    There is continuing controversy, extending into regulatory matters, over the significance to human health of positive results in carcinogenicity studies in animals using the gavage technique as the route of exposure. Our review of a nonrandom sample of 117 chemicals or chemical processes listed as known or reasonably anticipated to be carcinogenic in the National Toxicology Program's Third Annual Report on Carcinogens provides support for the validity of the gavage route in such studies. Twenty-three chemicals among the 117 substances and processes listed were positive by gavage. Twenty of these 23 chemicals were also appropriately studied by at least one other route of exposure. Thus, we were able to evaluate the extent to which positive gavage results were confirmed by another route of exposure in this sample. Nineteen (or 95%) of the twenty chemicals were positive for carcinogenicity by at least one other nongavage route in carcinogenicity bioassays. Moreover, in each of these 19 cases, positive carcinogenesis results were obtained by a nongavage route in the same species of animal where gavage administration led to the induction of cancer. All of the 23 gavage-positive chemicals induced tumors distal to the site of administration in at least one study, as did all 15 chemicals which were also positive by subcutaneous injection. We emphasize, however, the limited scope of our survey. We have not evaluated all chemicals that have tested positive by gavage and by at least one alternative route, nor have we assessed those chemicals found to be negative by the gavage route.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2707209

  5. Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies.

    PubMed Central

    Haseman, J K

    1984-01-01

    Statistical issues in the design, analysis and interpretation of animal carcinogenicity studies are discussed. In the area of experimental design, issues that must be considered include randomization of animals, sample size considerations, dose selection and allocation of animals to experimental groups, and control of potentially confounding factors. In the analysis of tumor incidence data, survival differences among groups should be taken into account. It is important to try to distinguish between tumors that contribute to the death of the animal and "incidental" tumors discovered at autopsy in an animal dying of an unrelated cause. Life table analyses (appropriate for lethal tumors) and incidental tumor tests (appropriate for nonfatal tumors) are described, and the utilization of these procedures by the National Toxicology Program is discussed. Despite the fact that past interpretations of carcinogenicity data have tended to focus on pairwise comparisons in general and high-dose effects in particular, the importance of trend tests should not be overlooked, since these procedures are more sensitive than pairwise comparisons to the detection of carcinogenic effects. No rigid statistical "decision rule" should be employed in the interpretation of carcinogenicity data. Although the statistical significance of an observed tumor increase is perhaps the single most important piece of evidence used in the evaluation process, a number of biological factors must also be taken into account. The use of historical control data, the false-positive issue and the interpretation of negative trends are also discussed. PMID:6525993

  6. The immune response of rat spleen to dietary fibers and to low doses of carcinogen: morphometric and immunohistochemical studies.

    PubMed

    Zusman, I; Gurevich, P; Benhur, H; Berman, V; Sandler, B; Tendler, Y; Madar, Z

    1998-01-01

    The effects of high-fiber diets on anticancer immune response are often masked by the effects of high-dose carcinogens. Using low levels of carcinogen the splenic immune response can be evaluated. Colon tumors were induced in rats with low doses of 1, 2-dimethylhydrazine, in the following experimental groups: rats fed with low fiber diet without exposure to carcinogen; rats exposed to the carcinogen and fed with low-fiber diet; rats exposed to carcinogen, and maintained on high-fiber diets, and did not develop tumors; and rats that developed tumors after exposure to carcinogen and maintenance on either low-fiber or high-fiber diets. After 24 weeks their spleens were studied immunohistochemically and morphometrically. In tumor-free rats, low doses of carcinogen caused significant response of the lymphoid system. This was manifested in the intensive blast transformation and in an increase in the number of dendritic cells and macrophages in different structures of the spleen. Dietary fibers activated these processes: the number of Ki-67 positive cells, macrophages and plasma cells increased significantly in the red pulp. A positive correlation was found between the effects of the carcinogen and proliferation of lymphocytes in the white pulp, and to lesser degree between high-fiber diets and lymphocytic abundance in the red pulp. The number of splenic apoptotic lymphocytes decreased in rats exposed to carcinogen. In tumor-bearing rats, immune insufficiency of the splenic responses was seen in the significant decrease of the areas of the mantle layer and the periarterial sheaths, as result of the decreased number of lymphocytes. Dietary fibers reduced the degree of this insufficiency. Even low doses of carcinogen cause a significant splenic immune response. This reaction has a compensatory character with macrophages, B and T cells participating. Addition of any high-fiber diet after the exposure to carcinogen activated the lymphocyte proliferation in the spleen. PMID

  7. Age-related light scattering in rat lenses observed in a 2-year inhalation toxicity study.

    PubMed

    Wegener, A; Kaegler, M; Stinn, W

    2002-01-01

    Normal light scattering in the eye is determined primarily by the size of alpha-crystalline molecules. Ageing effects appear as an increase in normal lens light scattering in distinct layers. Subliminal effects of toxins on lens transparency can also cause an increase in light scattering due to protein molecule aggregation before visible opacities appear. Scheimpflug photography of the anterior eye segment with subsequent densitometric image analysis is the method of choice to evaluate such effects. To gain more insight into normal ageing and the potential effects of complex aerosols, a subset of Wistar rats (both sexes) belonging to a larger chronic inhalation toxicity study was documented at baseline and after 2 years with a Topcon SL-45 Scheimpflug camera on Kodak T(max) 400 ISO film. The recording procedure, film development, and microdensitometric image analysis were all performed according to standard protocol. A second group from the same study was documented at the start and after 5 months of a 6-month posttreatment period immediately following the inhalation period. Rats were nose-only exposed for 6 h/day, 7 days/week, for 2 years to low (3 microg/l) or high (10 microg/l) concentrations of room-aged cigarette sidestream smoke or diesel engine exhaust. Control animals were exposed to filtered fresh air. At the baseline examination, there were no relevant differences between groups with respect to corneal density or density of defined layers in the lens capsule (1), epithelium and superficial cortex (2), deep cortex (3), supranuclear layer (4) and nucleus (5). At the 2-year examination, mean corneal density was significantly lower in females than in males. This same trend, although not significant, was also found in most layers of the lens. The most prominent differences in density over time were measured in lens layers 3 and 4, but neither corneal density nor lenticular density showed any consistent treatment-related effects in any of the layers. The data

  8. 2-year outcomes in Initial survivors with Acute Liver failure: Results from a Prospective, Multicenter Study

    PubMed Central

    Fontana, Robert J.; Ellerbe, Caitlyn; Durkalski, Valerie E.; Rangnekar, Amol; Reddy, K. Rajender; Stravitz, Todd; McGuire, Brendan; Davern, Timothy; Reuben, Adrian; Liou, Iris; Fix, Oren; Ganger, Daniel R; Chung, Raymond T.; Schilsky, Mike; Han, Steven; Hynan, Linda S.; Sanders, Corron; Lee, William M.

    2014-01-01

    BACKGROUND The long-term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. AIMS The aim of the current study is to provide an overview of the 2 year clinical outcomes amongst initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrollment in the Acute Liver Failure Study Group (ALFSG). METHODS Outcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed. RESULTS 2-year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non-APAP SS (75.5%) (p < 0.0001). The causes of death were similar in the 3 groups but the time to death was significantly longer in the LT recipients (p< 0.0001). Independent predictors of 2-year mortality in the APAP group were a high serum phosphate level and patient age (c-statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non-APAP group (c-statistic =0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c-statistic=0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (p < 0.05). CONCLUSIONS Two-year outcomes in initial survivors of ALF are generally good but non-APAP patients have a significantly lower survival which may relate to pre-existing medical co-morbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow-up from ongoing psychiatric and substance abuse issues. PMID:25039930

  9. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    SciTech Connect

    Oller, Adriana R. Kirkpatrick, Daniel T.; Radovsky, Ann; Bates, Hudson K.

    2008-12-01

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m{sup 3} nickel metal powder (MMAD = 1.8 {mu}m, GSD = 2.4 {mu}m) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m{sup 3} nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m{sup 3} was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m{sup 3} male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m{sup 3} females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies.

  10. Dual controls, p-value plots, and the multiple testing issue in carcinogenicity studies.

    PubMed Central

    Selwyn, M R

    1989-01-01

    The interpretation of statistically significant findings in a carcinogenicity study is difficult, in part because of the large number of statistical tests conducted. Some scientists who believe that the false positive rates in these experiments are unreasonably large often suggest that the use of multiple control groups will provide important insight into the operational false positive rates. The purpose of this paper is 2-fold: to present results from two carcinogenicity studies with dual control groups, and to present and illustrate a new graphical technique potentially useful in the analysis and interpretation of tumor data from carcinogenicity studies. The experimental data analyzed show that statistically significant differences between identically treated groups will occur with regular frequency. Such data, however, do not provide strong evidence of extrabinomial variation in tumor rates. The p-value plot is advocated as a graphical method that can be used to assess visually the ensemble of p values for neoplasm data from an entire study. This technique is then illustrated using several examples. Through computer simulation, we present p-value plots generated with and without treatment effects present. On average, the plots look substantially different depending on the presence or absence of an effect. We also evaluate decision rules motivated by the p-value plots. Such rules appear to have good power to detect treatment effects (i.e., have low false negative rates) while still controlling false positive rates. PMID:2676502

  11. Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 mice.

    PubMed

    Tillmann, Thomas; Ernst, Heinrich; Ebert, Sven; Kuster, Niels; Behnke, Wolfgang; Rittinghausen, Susanne; Dasenbrock, Clemens

    2007-04-01

    The purpose of this study using a total of 1170 B6C3F1 mice was to detect and evaluate possible carcinogenic effects in mice exposed to radio-frequency-radiation (RFR) from Global System for Mobile Communication (GSM) and Digital Personal Communications System (DCS) handsets as emitted by handsets operating in the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a period of 2 years to three different whole-body averaged specific absorption rate (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the organ-related tumor incidence, pairwise Fisher's test did not show any significant increase in the incidence of any particular tumor type in the RF exposed groups as compared to the sham exposed group. Interestingly, while the incidences of hepatocellular carcinomas were similar in EMF and sham exposed groups, in both studies the incidences of liver adenomas in males decreased with increasing dose levels; the incidences in the high dose groups were statistically significantly different from those in the sham exposed groups. Comparison to published tumor rates in untreated mice revealed that the observed tumor rates were within the range of historical control data. In conclusion, the present study produced no evidence that the exposure of male and female B6C3F1 mice to wireless GSM and DCS radio frequency signals at a whole body absorption rate of up to 4.0 W/kg resulted in any adverse health effect or had any cumulative influence on the incidence or severity of neoplastic and non-neoplastic background lesions, and thus the study did not provide any evidence of RF possessing a carcinogenic potential. PMID:17019729

  12. CARCINOGENICITY AND PESTICIDES: BIOLOGICAL ISSUES IN EXTRAPOLATION

    EPA Science Inventory

    Approximately 41% (26/63) of the pesticides evaluated in the chronic toxicity and carcinogen lofty studies of the National Toxicology Program (NTP) showed varying degrees of carcinogenicity. Since those chemicals nominated to the NTP for carcinogenicity studies usually represent ...

  13. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study

    PubMed Central

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  14. Learning, Memory, and Executive Function in New MDMA Users: A 2-Year Follow-Up Study.

    PubMed

    Wagner, Daniel; Tkotz, Simon; Koester, Philip; Becker, Benjamin; Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2015-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is associated with changes in neurocognitive performance. Recent studies in laboratory animals have provided additional support for the neurodegeneration hypothesis. However, results from animal research need to be applied to humans with caution. Moreover, several of the studies that examine MDMA users suffer from methodological shortcomings. Therefore, a prospective cohort study was designed in order to overcome these previous methodological shortcomings and to assess the relationship between the continuing use of MDMA and cognitive performance in incipient MDMA users. It was hypothesized that, depending on the amount of MDMA taken, the continued use of MDMA over a 2-year period would lead to further decreases in cognitive performance, especially in visual paired association learning tasks. Ninety-six subjects were assessed, at the second follow-up assessment: 31 of these were non-users, 55 moderate-users, and 10 heavy-users. Separate repeated measures analyses of variance were conducted for each cognitive domain, including attention and information processing speed, episodic memory, and executive functioning. Furthermore, possible confounders including age, general intelligence, cannabis use, alcohol use, use of other concomitant substances, recent medical treatment, participation in sports, level of nutrition, sleep patterns, and subjective well-being were assessed. The Repeated measures analysis of variance (rANOVA) revealed that a marginally significant change in immediate and delayed recall test performances of visual paired associates learning had taken place within the follow-up period of 2 years. No further deterioration in continuing MDMA-users was observed in the second follow-up period. No significant differences with the other neuropsychological tests were noted. It seems that MDMA use can impair visual paired associates learning in new users. However, the groups differed in their use of concomitant use of

  15. Effectiveness of a tinnitus management programme: a 2-year follow-up study

    PubMed Central

    Gudex, Claire; Skellgaard, Preben H; West, Torben; Sørensen, Jan

    2009-01-01

    Background Tinnitus impairs the possibility of leading a normal life in 0.5–1% of the population. While neither medical nor surgical treatment appears effective, counselling may offer some relief. An intervention combining counselling and hearing devices is offered to clients referred to the Centre for Help Aids and Communication (CHC) in southern Denmark. The aims of this exploratory study were to examine i) the characteristics of CHC's clients and their tinnitus, ii) the effectiveness of the treatment, and iii) whether particular client groups benefit more than others. Methods One hundred new clients presenting with tinnitus completed the Tinnitus Handicap Inventory (THI) three times – before their first consultation, after one month and after 1–2 years. The scores were tested for significant differences over time using tests for paired data. Logistic regression was used to examine factors associated with a clinically important difference (i.e. THI score improvement of at least 20 points). Results At final follow-up, total THI score was significantly lower than baseline, i.e. 29.8 (CI 25.5–34.2) vs. 37.2 (CI 33.1–37.2), p < 0.01. The programme achieved a clinically important difference for 27% and 24% of the clients one month and 1–2 years after the first consultation, respectively. It appeared that greater improvement in THI score was related to higher baseline THI score and possibly also to treatment by a particular CHC therapist. The absolute reduction in mean THI score after 1–2 years for clients with moderate and severe handicap was 14 and 20 points, respectively, i.e. similar to that previously reported for TRT (14–28 points). The cost of the current programme was approximately 200 EUR per client. Conclusion The tinnitus management programme appeared to provide significant benefit to many clients at a relatively low cost. It would be useful to conduct a randomised controlled study comparing the current programme with alternative forms of

  16. Stressful work, psychological job strain, and turnover: a 2-year prospective cohort study of truck drivers.

    PubMed

    de Croon, Einar M; Sluiter, Judith K; Blonk, Roland W B; Broersen, Jake P J; Frings-Dresen, Monique H W

    2004-06-01

    Based on a model that combines existing organizational stress theory and job transition theory, this 2-year longitudinal study examined antecedents and consequences of turnover among Dutch truck drivers. For this purpose, self-reported data on stressful work (job demands and control), psychological strain (need for recovery after work and fatigue), and turnover were obtained from 820 drivers in 1998 and 2000. In agreement with the model, the results showed that strain mediates the influence of stressful work on voluntary turnover. Also in conformity with the model, job movement to any job outside the trucking industry (i.e., interoccupational turnover) resulted in a larger strain reduction as compared to job movement within the trucking industry (intraoccupational turnover). Finally, strain was found to stimulate interoccupational turnover more strongly than it stimulated intraoccupational turnover. These findings provide a thorough validation of existing turnover theory and give new insights into the turnover (decision) process. PMID:15161404

  17. Occlusal glass ionomer cermet, resin sandwich and amalgam restorations: a 2-year clinical study.

    PubMed

    Lidums, A; Wilkie, R; Smales, R

    1993-08-01

    This study compared the clinical behavior of a glass ionomer silver cermet (Ketac-Silver), a posterior resin composite (Visio-Molar) used with the "sandwich" technique, and a high-copper amalgam (Dispersalloy) for restoring conventional Class I occlusal cavity preparations. Two dentists placed 116 restorations in the posterior permanent teeth of 35 adults treated at a dental hospital. Restorations were assessed at 6-month intervals over 2 years for bulk loss of material and occlusal wear, surface voids, roughness and cracking, surface and marginal staining, and marginal fracture. Losses of material and surface voids were obvious with the cermet material, with surface crazing or cracking being present in 33% of the restorations. The cermet cannot be recommended as a long-term permanent restorative material if the restorations are likely to be subjected to heavy occlusal stresses and abrasive wear. PMID:7803005

  18. [Influence of sport on isoinertial trunk muscle performance development: a 2 years prospective study].

    PubMed

    Rosset, E Bibbo; Mélot, C; Szpalski, M; Keller, T S; Balagué, F

    2013-07-17

    In this study, we investigate the relationship between either regular sports practice or a non sportive way of life, development of trunk muscle performance and occurrence of lower back pain between male schoolchildren. 93 schoolchildren were recruited, then stratified in 4 groups, according to sport practice or sedentary way of life. Participants were evaluated twice at an interval of 2 years with an interview, a physical examination and an evaluation of trunk muscle performance. We identified that basketball players have significantly better results and perfomance concerning isometric and isoinertial tests of trunk muscles than the other groups. Differences in trunk muscle performance exist following the practice of different types of sport. We can deduce that trunk muscle performance has some sport specificity. PMID:23971327

  19. A 2-year longitudinal study of prospective predictors of pathological Internet use in adolescents.

    PubMed

    Strittmatter, Esther; Parzer, Peter; Brunner, Romuald; Fischer, Gloria; Durkee, Tony; Carli, Vladimir; Hoven, Christina W; Wasserman, Camilla; Sarchiapone, Marco; Wasserman, Danuta; Resch, Franz; Kaess, Michael

    2016-07-01

    Longitudinal studies of prospective predictors for pathological Internet use (PIU) in adolescents as well as its course are lacking. This three-wave longitudinal study was conducted within the framework of the European Union-funded project "Saving and Empowering Young Lives in Europe" over a 2-year period. The sample consisted of 1444 students at the baseline investigation (T0); 1202 students after 1 year (T1); and 515 students after 2 years (T2). Structured self-report questionnaires were administered at all three time points. PIU was assessed using the Young Diagnostic Questionnaire (YDQ). In addition, demographic (i.e., gender), social (i.e., parental involvement), psychological (i.e., emotional problems), and Internet use-related factors (i.e., online activities) were assessed as prospective predictors. The prevalence of PIU was 4.3 % at T0, 2.7 % at T1 and 3.1 % at T2. However, only 3 students (0.58 %) had persistent categorical PIU (YDQ score of ≥5) over the 2-year period. In univariate models, a variety of variables that have been previously identified in cross-sectional investigations predicted PIU at T2. However, multivariate regression demonstrated that only previous PIU symptoms and emotional problems were significant predictors of PIU 2 years later (adjusted R (2) 0.23). The stability of categorical PIU in adolescents over 2 years was lower than previously reported. However, current PIU symptoms were the best predictor of later PIU; emotional symptoms also predicted PIU over and above the influence of previous problematic Internet use. Both PIU symptoms and emotional problems may contribute to the vicious cycle that supports the perpetuation of PIU. PMID:26526444

  20. Study of 2 years follow-up of referral patients with abnormal Pap smear

    PubMed Central

    Behnamfar, Fariba; Zafarbakhsh, Azam; Allameh, Taj-Alsadat

    2015-01-01

    Background: Abnormal Pap smear consists of premalignant or malignant cervical lesions. Many of premalignant cervical lesions will never progress to invasive malignancy, or even may regress over the time. Thus, there is always a risk of overtreatment of patients with an abnormal Pap smear. A long-term follow-up of these patients can reveal final events associated with each subtype of abnormal Pap smear, and, therefore, help us to prevent unnecessary interventions. The aim of our study was to present 2 years follow-up of referral patients with abnormal Pap smear. Materials and Methods: A total of 334 consecutive women aged more than 16 who were referred with an abnormal Pap smear were entered into the study. Patients were followed with biannual Pap smear and annual colposcopy and biopsy for 2 years. Results: At baseline, the majority of patients with abnormal Pap smear were normal on colposcopy and biopsy (68% and 86%, respectively). Six months after first abnormal Pap smear majority of patients in each group showed a significant regress to normal or less invasive lesion (P < 0.001). Twelve patients (4%) had no change in Pap smear, whereas 313 (94%) had at least one stage improvement. Only nine (3%) patients had deteriorated Pap smear after 6 months. All 308 patients who underwent colposcopy and biopsy had normal Pap smear 24 months after the first abnormal Pap smear. Conclusion: Pap smear is associated with a high rate of false-positive results. In addition, the majority of low-grade cervical lesions can spontaneously regress. A long-term follow-up of a patient with abnormal Pap smear can help us to avoid needless interventions. PMID:26958048

  1. An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program.

    PubMed Central

    Chhabra, R S; Huff, J E; Schwetz, B S; Selkirk, J

    1990-01-01

    Since the establishment of the National Toxicology Program (NTP), there have been gradual changes in strategies to evaluate the overall toxicity of chemicals as well as their carcinogenic potential. The spectrum of toxicologic information sought on selected chemicals has been broadened by the multidisciplinary approach to evaluating chemicals. This paper describes the scientific rationale and experimental processes used by NTP in designing studies. Also, an outline of current NTP protocols are given for prechronic and chronic toxicity/carcinogenicity studies. PMID:2205492

  2. Suitability of Chinese oil well loggers for an epidemiologic study of the carcinogenic effects of neutrons.

    PubMed

    Inskip, P D; Wang, Z Y; Fen, Y S

    1991-11-01

    Neutron exposures to 191 well loggers at four oil fields in China were measured over a 3-mo period using CR-39 polycarbonate dosimeters. Doses (96% less than 0.02 mGy) were slightly lower than literature values for well loggers in North America, possibly because of differences in drilling activity. Because doses are so low, an epidemiologic study of cancer among Chinese well loggers is unlikely to be informative about the carcinogenicity of neutrons relative to sparsely ionizing radiation. PMID:1752747

  3. Residue level and dissipation pattern of spiromesifen in cabbage and soil from 2-year field study.

    PubMed

    Siddamallaiah, Lekha; Mohapatra, Soudamini

    2016-03-01

    Spiromesifen is a new class of insecticide used for the control of whiteflies and mites which have developed resistance to the more commonly used neonicotinoids. Dissipation pattern of spiromesifen on cabbage was evaluated over 2 years by conducting supervised field studies as per good agricultural practices. Cabbage and soil samples were extracted and purified using modified QuEChERS method and analyzed through gas chromatography (GC). Confirmatory studies were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The recoveries of spiromesifen from cabbage and soil were between 85.44 and 103.37% with the relative standard deviation (RSD) between 3.2 and 9.4% (n = 6). The limit of detection (LOD) and limit of quantification (LOQ) were 0.003 μg mL(-1) and 0.01 mg kg(-1), respectively. The measurement uncertainties (MUs) were within 9.9-14.9%. Initial residues of spiromesifen on cabbage were 0.640 and 1.549 mg kg(-1) during 2013 and 0.723 and 1.438 mg kg(-1) during 2014 from treatments at standard and double doses of 125 and 250 g active ingredient (a.i.) ha(-1), respectively. Spiromesifen residue dissipation followed first-order rate kinetics, and it degraded within the half-lives of 2.9 and 3.9 days during 2013 and 3.2 and 4.5 days during 2014. The residue levels reached below the maximum residue limit (MRL; 0.02 mg kg(-1)) within 15-17 days at the standard dose and 24-27 days at the double dose. The field soil analyzed at harvest (30 days) was free from spiromesifen residues. Metabolite spiromesifen-enol was not detected in any sample which was confirmed through LC-MS/MS analysis. PMID:26869045

  4. Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations

    SciTech Connect

    Dasenbrock, Clemens . E-mail: clemens-dasebrock@bc.boehringer-ingelheim.com

    2005-09-01

    Since a report in 1997 on an increased lymphoma incidence in mice chronically exposed to a mobile phone radiofrequency signal, none of the subsequent long-term studies in rodents have confirmed these results. On the other hand, several of the follow-up co- and carcinogenicity studies are still underway or are presently being initiated. Most of the published long-term studies used 1 exposure level only and suffer from a poor dosimetry which does not consider the animal's growth. Additional points of criticism are a limited, in some cases, questionable histopathology and inadequate group sizes. Overall, if dealing with new chemicals or drugs, these studies would not be acceptable for registration with the responsible authorities. The major critical points are taken into consideration within the European co- and carcinogenicity projects (CEMFEC and PERFORM-A), which are in their final stages and in the US long-term studies in mice and rats which are about to be initiated. Nevertheless, the WHO evaluation for health risk assessment of long-term telephone use and base station exposure will start in late 2005.

  5. Ankle Sprain Injuries: A 2-Year Prospective Cohort Study in Female Greek Professional Basketball Players

    PubMed Central

    Kofotolis, Nikolaos; Kellis, Eleftherios

    2007-01-01

    Context: Ankle sprains are a common basketball injury. Therefore, examination of risk factors for injury in female professional basketball players is worthwhile. Objective: To examine rates of ankle sprains, associated time missed from participation, and risk factors for injury during 2 consecutive seasons. Design: Prospective cohort study. Setting: Eighteen professional basketball facilities. Patients or Other Participants: We observed 204 players from 18 female professional basketball teams for 2 consecutive seasons during a 2-year period. Main Outcome Measure(s): Using questionnaires, we recorded the incidence of ankle sprains, participation time missed, and mechanisms of injury in games and practice sessions. Potential risk factors, such as age, body mass, height, training experience, and history of ankle sprain, were examined using multivariate logistic regression. Results: Fifty of the 204 participants sustained ankle injuries; injuries included 32 ankle sprains, which translated to an ankle sprain rate of 1.12 per 1000 hours of exposure to injury. The 32 players missed 224.4 training and game sessions and an average of 7.01 sessions per injury. Most injuries occurred in the key area of the basketball court and were the result of contact. Injury rates during games were higher than injury rates during practice sessions. Centers, followed by guards and forwards, had the highest rate of injury. Players who did not wear an external ankle support had an odds ratio of 2.481 for sustaining an ankle sprain. Conclusions: Female professional basketball athletes who did not wear an external ankle support, who played in the key area, or who functioned as centers had a higher risk for ankle sprain than did other players. PMID:18059995

  6. Monitoring Cyp2b10 mRNA expression at cessation of 2-year carcinogenesis bioassay in mouse liver provides evidence for a carcinogenic mechanism devoid of human relevance: The dalcetrapib experience

    SciTech Connect

    Hoflack, J-C.; Mueller, L. Fowler, S.; Braendli-Baiocco, A.; Flint, N.; Kuhlmann, O.; Singer, T.; Roth, A.

    2012-03-15

    Introduction: Dalcetrapib is a cholesteryl ester transfer protein (CETP) modulator in clinical assessment for cardiovascular outcome benefits. In compliance with regulatory requirements, dalcetrapib was evaluated in rodent 2-year carcinogenesis bioassays. In the mouse bioassay, male mice demonstrated increased liver weight and statistically increased incidences of hepatocellular adenoma/carcinoma. Hepatic cytochrome p450 (Cyp) 2b10 mRNA induction and increased Cyp2b10 enzyme activity signify activation of hepatic nuclear receptor constitutive androstane receptor (CAR), a widely established promoter of rodent-specific hepatic tumors. We therefore monitored hepatic Cyp2b10 mRNA and its enzyme activity in a subset of dalcetrapib-treated male mice from the bioassay. Methods: Liver samples were obtained from ∼ 1/3 of male mice from each dose group including vehicle-controls (mean and earliest study day of death 678 and 459 respectively). Quantitative real time PCR (qRT-PCR) was performed to determine Cyp2b10 mRNA expression and Cyp1a-, Cyp2b10- and Cyp3a-selective activities were monitored. Results: Cyp2b10 mRNA was strongly induced by dalcetrapib with an expected wide inter-individual variation (5–1421-fold). Group average fold-induction versus vehicle-controls showed a dose-related increase from 48-fold (250 mg/kg/day) to 160-fold (750 mg/kg/day), which declined slightly at 2000 mg/kg/day (97-fold). Cyp enzyme activities showed approximate doubling of total Cyp P450 content per milligram protein and a 9-fold increase in Cyp2b10-selective pentoxyresorufin O-dealkylase activity (750 mg/kg/day). Discussion: These data from hepatic Cyp2b10 monitoring are strongly suggestive of CAR activation by dalcetrapib, a mechanism devoid of relevance towards hepatocarcinogenesis in humans; results show feasibility of Cyp2b10 as a surrogate marker for this mechanism at cessation of a carcinogenesis bioassay. -- Highlights: ► Liver tumors were induced in male mice by dalcetrapib

  7. Mutagenicity and carcinogenicity studies of homemade rust-proof cutting fluid

    SciTech Connect

    Wang, D.; Huang, W.Q.; Wang, H.W.

    1988-01-01

    A homemade rust-proof cutting fluid (RPCF) used in China was tested for carcinogenicity by an in vivo chronic experiment and for mutagenicity by the Ames Salmonella microsomal assay. Undiluted and threefold water-diluted fluid were given as drinking water to groups of young adult Wistar rats for 2 years. The treatment induced 11/40 malignant tumors with 9/40 acinar adenocarcinomas of the pancreas in the high-dose group. Simultaneous administration of ascorbic acid dissolved in the undiluted fluid at 2 g acid per 1 g sodium nitrite resulted in 1/40 pancreatic carcinoma. The results of the Ames test showed that the technical RPCF was mutagenic to TA100 with or without metabolic activation. It was concluded that the homemade RPCF, which is comprised of sodium nitrite, triethanolamine, and polyethylene glycol, may form direct-acting mutagen(s) upon storage and form, in vivo, e.g., nitrosamines that caused acinar pancreatic carcinoma in Wistar rats. Simultaneous administration of ascorbic acid is suggested for the protection of workers exposed to the rust-proof cutting fluid.

  8. The retrospective study of the carcinogenic hydrocarbon benz[a]pyrene in the biosphere.

    PubMed

    Ilnitsky, A P; Vinogradov, V N; Riabchun, V K; Mischenko, V S; Gvildis, V Y; Belitsky, G A; Shabad, L M

    1979-11-01

    The major aim of this study was to determine taking, as an example, the carcinogenic polycyclic aromatic hydrocarbon benz[a]pyrene (BaP), the present biologically active compounds in the early historical and geological epochs with the following assessment of the degree of danger of such compounds in the modern times. In the first section of work, study results of soil samples in the areas of eternal frost confirmed the presence of BaP in the frozen layers of soil aged 10 years, 100 years, 3000--4000 and 10,000 years of age. In the second part of the work, results are furnished on the BaP content in the ice of modern glaciers and their moraines, located in Kamchatka. BaP was found in 11 samples in the concentration of 0.001--0.003 microgram/l. These data represent the first results in the retrospective study of carcinogenic substances in the biosphere. PMID:509419

  9. Are genotoxic carcinogens more potent than nongenotoxic carcinogens?

    PubMed Central

    Parodi, S; Malacarne, D; Romano, P; Taningher, M

    1991-01-01

    In this report we have raised the question whether genotoxic carcinogens are more potent than nongenotoxic carcinogens when studied in long-term carcinogenicity assays in rodents. To build a large database of compounds for which both carcinogenicity and genotoxicity had been investigated, we have used a database produced by Gold and co-workers for carcinogenic potency data (975 chemicals) and a database produced by Würgler for genotoxicity data (2834 chemicals). Considering compounds positive or negative in at least three short-term tests and in at least 75% of available tests, we could define 67 genotoxic carcinogens and 46 nongenotoxic carcinogens. Carcinogenic potency of genotoxic carcinogens was about 50 times higher than carcinogenic potency of nongenotoxic carcinogens. Our results are different from the results of Tennant et al.; their database (24 genotoxic carcinogens and 12 nongenotoxic carcinogens compatible with our definition) seems to suggest that there is practically no difference in potency between genotoxic and nongenotoxic carcinogens. The two databases have only four compounds in common and are also different in terms of number of elements for different chemical classes. Nitrosocompounds, nitrogen mustards, hydrazine derivatives, and polycyclic aromatic hydrocarbons are not represented in the database of Tennant. The overall impression from our analysis is that the usefulness of short-term tests of genotoxicity could be significantly better than what has been suggested by the previous work of Tennant et al. because these tests tend to detect, at least for many important chemical classes, the most potent carcinogens. This consideration may not be valid for certain classes of chemicals. PMID:1821372

  10. Experience from a long-term carcinogenicity study with intraperitoneal injection of biosoluble synthetic mineral fibers.

    PubMed

    Grimm, Hans G; Bernstein, David M; Attia, Mahmoud; Richard, Jacques; De Reydellet, Aymon

    2002-08-01

    The carcinogenic potential in the intraperitoneal cavity of three newly developed biosoluble insulation glass wool fibers (M, P, and V) and one newly developed biosoluble insulation stone wool fiber (O) was investigated and compared to that of a previously developed soluble glass fiber (B). The in vitro dissolution coefficient of the three glass wool fibers ranged from 450 to 1037 ng/cm(2) x h and was 523 ng/cm(2) x h for the stone wool fiber. The in vitro dissolution coefficient of the B fiber was 580 ng/cm(2) x h. Groups of female Wistar rats (strain Crl: Wi BR) were exposed by repeated injections to doses of 0.5, 2, and 5 x 10(9) WHO fibers, which corresponds to between 41 mg to 724 mg fiber injected. In addition, 2 groups of crocidolite were used as positive controls at doses of 0.1 x 10(9) and 1 x 10(9) WHO fibers (0.5 and 5 mg). The in vitro dissolution coefficient of crocidolite is estimated to be approximately 1 ng/cm(2) x h. The protocol of the study and the size distribution of the test samples conformed to the European Commission Protocol EUR 18748 EN, and the study was executed under Good Laboratory Practice conditions. Two of the new insulation wools, fibers M and 0, showed no statistically significant tumorigenic response even at the very high dose of 5 x 10(9) WHO fibers injected. Fibers P and V showed a small tumorigenic response in the ip cavity similar in magnitude to the B fiber, which has been declared in the German fiber regulations as a noncarcinogenic fiber. The response to the soluble insulation fibers was notably different from that of the known carcinogen crocidolite, which produced 53% tumors at a comparatively low dose of 0.1 x 10(9) WHO fibers. The incidence of mesothelioma was found to be highly correlated to the incidence of intra-abdominal nodules and masses at different sites. The incidence of abdominal nodules and masses was highly correlated to the number of animals with ascites. The incidence of chronic peritonitis with fibrotic

  11. Asbestos use and carcinogenicity in Germany and a comparison with animal studies.

    PubMed

    Pott, F

    1994-08-01

    The centralized structure of economic affairs in the former German Democratic Republic (East Germany) and the isolation from the free market led to the situation that imported asbestos was almost exclusively chrysotile. More than 90% came from the Kiembay mining area in the Ural Mountains, and about 7% was long-fibre chrysotile from Canada. Sturm and co-workers detected 1082 mesothelioma cases from 1960 to 1990 in the counties of Magdeburg and Halle. In 843 of these cases an exposure to asbestos was evident. Seventy-two cases were exposed to chrysotile only. Suspected exposure to amphiboles imported before World War II or to fibre contained in talc could not be substantiated. Up to now, there have been no analyses of lung fibre burdens from such cases. Reviewing the carcinogenicity studies in rats performed by inhalation or intra-cavitary injection of chrysotile, amosite and crocidolite fibres, the results give no clear indication of a lower carcinogenic potency per chrysotile fibre than per amphibole fibre if equal fibre numbers and fibre sizes are applied, although the chrysotile content of the lungs is relatively low. Also the mesothelioma rates after inhalation exposure to extremely high concentrations of the different asbestos fibre types are similar for chrysotile and the amphiboles and in the region of 5%. Compared with the asbestos-related cancer rates in chrysotile textile workers, rats have to be exposed to a more than 100-fold higher fibre concentration than humans to induce the same lung tumour incidence. PMID:7978982

  12. Carcinogen File.

    ERIC Educational Resources Information Center

    Environment, 1978

    1978-01-01

    First in a series of bulletins designed to provide information about the problem of carcinogens in the environment is on benzo(a)pyrine. Benzo(a)pyrine is a proven cancer-causing substance that has been known for over ten years to occur in broiled sausages, gas-broiled fish and beef steak, and charcoal-broiled meat. (Author/BB)

  13. A comparative study of systemic carcinogen exposure in waterpipe smokers, cigarette smokers and non-smokers

    PubMed Central

    Al Ali, Radwan; Rastam, Samer; Ibrahim, Iman; Bazzi, Asma; Fayad, Sanaa; Shihadeh, Alan L; Zaatari, Ghazi S; Maziak, Wasim

    2014-01-01

    Background In the past decade, waterpipe smoking—also known as hookah, shisha, narghileh—has increased among youth. The scarcity of rigorous studies linking waterpipe smoking to smoking-related diseases has hindered policy and regulatory efforts to confront the waterpipe epidemic. This study compares systemic carcinogen exposure between independent groups of exclusive waterpipe smokers, cigarette smokers and nonsmokers. Methods This study was conducted at the Syrian Center for Tobacco Studies (SCTS) in Aleppo, Syria, between 2010 and 2011. First morning urinary samples were collected from three groups of subjects; exclusive daily waterpipe smokers (n=24), exclusive daily cigarette smokers (n=23), and non-smokers (n=28). These samples were analysed for carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) using liquid chromatography—tandem mass spectrometry (LC-MS/MS). Results Our results show that waterpipe smokers are exposed to about 5–10 times greater NNAL than nonsmokers. Mean (95% CI) free and total NNAL was 0.7 (0.3 to 1. 4) and 3.9 (1.6 to 9.5) pg/mL urine for nonsmokers, 8.4 (4.8 to 14.8) and 33.0 (21.6 to 50.6) pg/mL urine for waterpipe smokers, and 10.7 (5.0 to 22.6) and 46.8 (27.6 to 79.3) pg/mL urine for cigarette smokers (p<0.001 for all comparisons). Daily waterpipe smokers were less exposed to NNAL than daily cigarette smokers, although the difference did not reach statistical significance for all measurements. Conclusions These results provide the clearest indication to date about systemic exposure to harmful carcinogens associated with long-term waterpipe smoking. Such evidence can support policy and regulatory efforts designed to confront the emerging global waterpipe epidemic, as well as drive interventions aimed at increasing the public awareness about the cancer risk associated with waterpipe smoking. PMID:23988862

  14. Carcinogenicity of inhaled nanoparticles.

    PubMed

    Roller, Markus

    2009-07-01

    Large epidemiological studies in the United States have shown a statistical association between air concentration of the fine dust fraction PM(2.5) in the general environment and increased risk of lung cancer. A quantitative risk assessment for lung cancer based on these studies corresponds to risk estimates based on studies at workplaces with exposure to diesel engine emissions; its magnitude cannot be explained by the known carcinogenicity of organic substances or metals adsorbed to the insoluble particle core. Carcinogenic effects of diesel particles were observed after inhalation in rats independently in several studies. The surprisingly strong effect of diesel particles was partially attributed to their small size. This hypothesis was corroborated by inhalation studies with synthetic nanoparticles virtually free of organic compounds. IARC found sufficient evidence for the carcinogenicity of carbon black and of titanium dioxide in experimental animals. Long-term studies by the method of intratracheal instillation confirmed the carcinogenic effects in rats for an even broader spectrum of synthetic nanoparticles. Non-positive studies with hamsters are not valid because hamsters did not develop lung tumors after inhalation of some known human carcinogens. In recent years, the number of publications reporting in vitro genotoxicity of TiO(2) and of carbon black nanomaterials has increased. Overall, there is clear positive evidence for carcinogenicity in rats, together with supporting evidence from human data of structurally related substances. Therefore, the European Union (EU) criteria for category 2 of carcinogenic substances appear to be fulfilled for bio-durable nanoparticles consisting of matter without known significant specific toxicity. PMID:19558247

  15. Comparative toxicity and carcinogenicity studies of tetracycline and oxytetracycline in rats and mice.

    PubMed

    Dietz, D D; Abdo, K M; Haseman, J K; Eustis, S L; Huff, J E

    1991-08-01

    Two-year toxicity and carcinogenicity studies of oxytetracycline hydrochloride and tetracycline hydrochloride, two structurally similar and widely used antibiotics, were performed in F344/N rats and B6C3F1 mice. Rats and mice were continuously exposed via their diet to the following levels of antibiotic: oxytetracycline HCl--rats 0, 25,000, or 50,000 ppm; mice 0,6,300, or 12,500 ppm; tetracycline HCl--rats and mice 0, 12,500, or 25,000 ppm. On a milligram per kilogram of body weight basis these exposures represent doses that are 20 to 140 times daily human therapeutic doses. Dose-related increased survival was noted among oxytetracycline-treated male rats and tetracycline-treated female rats and male mice, while treatment-related reduced body weight gain occurred in oxytetracycline- and tetracycline-treated mice. Microscopic changes included fatty metamorphosis and focal cellular change in livers of oxytetracycline-treated male rats and basophilic cytoplasmic and clear cell change in livers of tetracycline-treated male rats. The only neoplastic changes were a marginally increased trend in pheochromocytoma of the adrenal medulla (equivocal evidence only) among oxytetracycline-exposed male rats (12/50 controls, 19/50 low dose, 24/50 high dose) and an increased incidence of pituitary adenoma or adenocarcinoma among high-dose oxytetracycline-treated female rats (20/50 controls, 32/50 high dose). Although oxytetracycline and tetracycline appeared to increase the incidence of pituitary hyperplasia in high-dose male and female rats, respectively, the total incidence of proliferative changes (hyperplasia, adenoma, and adenocarcinoma) was not affected by antibiotic exposure. The results from these studies therefore support the notion that neither antibiotic is carcinogenic in rodents. There were several negative trends suggesting possible protective effects by both these tetracycline analogs against certain spontaneous neoplastic and non-neoplastic changes. PMID:1765221

  16. The in vivo rodent test systems for assessment of carcinogenic potential.

    PubMed

    van der Laan, Jan-Willem; Spindler, Per

    2002-02-01

    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic of discussion was pros and cons of the short- and medium-term models being evaluated by the ILSI-HESI project, in particular the usefulness of the models in relation to results of genotoxicity assays. Further discussions were advised following publication of the ILSI-HESI database, which is expected before the end of 2001. The use of the short- and medium-term rodent test systems were not considered appropriate for the assessment of carcinogenic potential of biotechnology-derived medicinal products. PMID:11846641

  17. Prescription Disposal Practices: A 2-Year Ecological Study of Drug Drop Box Donations in Appalachia

    PubMed Central

    Hagemeier, Nicholas; Brooks, Billy; Alamian, Arsham

    2015-01-01

    Objectives. We quantified controlled substance donations via permanent drug donation boxes over 2 years in a region with high prescription abuse, assessing medication characteristics, time between dispensing and donation, and weight of medications donated per capita. Methods. In partnership with Drug Enforcement Administration and local law enforcement, we analyzed permanent drug donation box collections in 8 Northeast Tennessee locations from June 2012 to April 2014. We recorded controlled substance dosage units along with the product dispensing date. Results. We collected 4841 pounds of pharmaceutical waste, 4.9% (238.5 pounds) of which were controlled substances, totaling 106 464 controlled substance doses. Analysis of dispensing dates for controlled substances indicated a median of 34 months lapsed from dispensing to donation (range = 1–484 months). The mean controlled substance donation rate was 1.39 pounds per 1000 residents. Communities with fewer than 10 000 residents had a statistically higher controlled substance donation rate (P = .002) compared with communities with 10 000 or more residents. Conclusions. Permanent drug donation boxes can be an effective mechanism to remove controlled substances from community settings. Rural and urban community residents should be provided convenient and timely access to drug disposal options. PMID:26180956

  18. Significance of durability of mineral fibers for their toxicity and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of inhalation studies.

    PubMed Central

    Pott, F; Roller, M; Kamino, K; Bellmann, B

    1994-01-01

    At the same time that carcinogenicity of very thin glass fibers after intrapleural and intraperitoneal (ip) administration was demonstrated (1,2) researchers found that gypsum fibers and HCI-leached chrysotile fibers were easily soluble in the peritoneal cavity. This led to the conclusion that the chemical composition of fibers was not responsible for the carcinogenesis but that the degree of carcinogenic potency of a fiber depended on the extent to which it retained its fibrous structure. A thin glass fiber with a low biodurability did not induce tumors after ip injection of a high dose, although the ip test had been criticized for being "overly sensitive." The ip model has been the most successful for determining carcinogenicity of inorganic fibers and establishing dose-response relationships; but to determine the possibilities and limitations of this test model, very high doses of nonfibrous silicon carbide and of a slightly durable glass fiber type were injected ip in Wistar rats. No obviously acute or chronic toxic effect was observed in 90 weeks, but there was a 40% incidence of serosal tumors in the group treated with glass fibers. A pilot study on the persistence of slag fibers in the omentum of rats after ip injection showed a half-time of about 1 year. It was calculated that an ip injection of 10(9) fibers would lead to a concentration of fiber numbers in the ash of the omentum in the same range as the concentration in the lung after 2 years of inhalation exposure. The long-term inhalation study with fibers in rats has been called the "gold standard" for risk characterization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882919

  19. Stability and Change among High-Functioning Children with Pervasive Developmental Disorders: A 2-Year Outcome Study.

    ERIC Educational Resources Information Center

    Starr, Elizabeth; Szatmari, Peter; Bryson, Susan; Zwaigenbaum, Lonnie

    2003-01-01

    This study compared the 2-year outcomes of 68 children diagnosed with autism or Asperger syndrome at age 6-8 years in terms of symptoms from the Autism Diagnostic Interview. Significant differences were seen in the domains of social interaction, communication, and repetitive activities, with the Asperger group demonstrating fewer and/or less…

  20. EXPOSURE METHODOLOGIES AND SYSTEMS FOR LONG-TERM CHEMICAL CARCINOGENICITY STUDIES WITH SMALL FISH SPECIES

    EPA Science Inventory

    Testing waterborne chemical carcinogens in fish models requires accurate, reliable, and reproducible exposures. Because carcinogenesis is a chronic toxicological process and is often associated with prolonged latency periods, systems must accommodate lengthy in-life test periods ...

  1. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

    PubMed

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder

  2. Sluggish Cognitive Tempo and ADHD Inattention as Predictors of Externalizing, Internalizing, and Impairment Domains: A 2-Year Longitudinal Study.

    PubMed

    Bernad, Maria del Mar; Servera, Mateu; Becker, Stephen P; Burns, G Leonard

    2016-05-01

    Although sluggish cognitive tempo (SCT) is distinct from attention-deficit/hyperactivity disorder inattention (ADHD-IN), few studies have examined whether SCT longitudinally predicts other symptom or impairment dimensions. This study used 4 sources (mothers, fathers, primary teachers, and secondary teachers) and 3 occasions of measurement (first, second, and third grades) with 758 first grade (55 % boys), 718 second grade (54 % boys), and 585 third grade (53 % boys) children from Spain to determine SCT's and ADHD-IN's unique longitudinal relationships with psychopathology, academic impairment, and social impairment over the 1- and 2-year intervals (i.e., first to third grade, second to third grade). For 1- and 2-year intervals using both mothers' and fathers' ratings, higher levels of SCT uniquely predicted higher levels of anxiety, depression, academic impairment, and social impairment whereas higher levels of ADHD-IN uniquely predicted higher levels of ADHD-HI, ODD, and academic impairment. For 1- and 2-year intervals across different primary and secondary teachers (i.e., first/second and third grade ratings were provided by different teachers), higher scores on ADHD-IN uniquely predicted poorer outcomes across domains whereas higher scores on SCT uniquely predicted lower levels of ADHD-HI and ODD for both intervals in addition to higher levels of depression (for primary teachers only), academic impairment (for 1-year interval only), and peer rejection (2-year interval only for primary teachers). Overall, SCT was significantly associated with important outcomes independent of ADHD-IN over 1- and 2-year intervals and across four different raters. This study provides further evidence for distinguishing between SCT and ADHD-IN in home and school settings. PMID:26278273

  3. Carcinogenicity studies after intraperitoneal injection of two types of stone wool fibres in rats.

    PubMed

    Kamstrup, O; Ellehauge, A; Collier, C G; Davis, J M G

    2002-03-01

    A summary is given of the pathology results after intraperitoneal (i.p.) injection in rats of insulation wool HT, representing the new biosoluble types. The pathology results are compared with a previously conducted i.p. study with traditional stone wool D6 (with similar chemical composition to MMVF21). The HT fibre is characterized by a relatively high content of aluminium and a relatively low content of silica compared to MMVF21. HT has a high in vitro dissolution rate at pH 4.5, a relatively low dissolution rate at pH 7.5 and is less biopersistent than the MMVF21 fibre. Female Wistar rats received a dose of 2 x 10(9) WHO HT fibres by i.p. injection. The fibres had been size-selected to be largely rat respirable. The negative control group was exposed to saline. Following exposure, the animals were maintained until survival in one group fell below 20%. At this time, all animals were killed. All animals were subjected to a necropsy examination; any gross abnormalities observed at necropsy were subjected to histopathological examination. In addition, histopathology was carried out on a predefined list of tissues. The incidences of lesions and survival in the control and fibre dosed animals were compared using appropriate statistical methods to determine whether the dosed animals showed adverse effects on survival or a positive carcinogenic response. The main protocol for the previously conducted study with D6 (MMVF21) was similar, but the animals were maintained as long as they survived, and the WHO fibre dose was lower. The results of the comparative study showed a marked difference in the i.p. pathogenicity of D6 (MMVF21) and HT in terms of their carcinogenic potential. D6 (MMVF21) caused a statistically significant increase of mesotheliomas in the peritoneal cavity compared to the negative control, but the HT fibre did not cause any mesotheliomas or any increase in other tumour types. PMID:12074022

  4. Clinical and biochemical studies support smokeless tobacco's carcinogenic potential in the human oral cavity.

    PubMed

    Mallery, Susan R; Tong, Meng; Michaels, Gregory C; Kiyani, Amber R; Hecht, Stephen S

    2014-01-01

    In 2007, the International Agency for Research on Cancer presented compelling evidence that linked smokeless tobacco use to the development of human oral cancer. Although these findings imply vigorous local carcinogen metabolism, little is known about levels and distribution of phase I, II, and III (drug egress) enzymes in human oral mucosa. In this study here, we integrated clinical data, and imaging and histopathologic analyses of an oral squamous cell carcinoma that arose at the site of smokeless tobacco quid placement in a patient. Immunoblot and immunohistochemical (IHC) analyses were used to identify tumor and normal human oral mucosal smokeless tobacco-associated metabolic activation and detoxification enzymes. Human oral epithelium contains every known phase I enzyme associated with nitrosamine oxidative bioactivation with approximately 2-fold interdonor differences in protein levels. Previous studies have confirmed approximately 3.5-fold interdonor variations in intraepithelial phase II enzymes. Unlike the superficially located enzymes in nonreplicating esophageal surface epithelium, IHC studies confirmed that oral mucosal nitrosamine metabolizing enzymes reside in the basilar and suprabasilar region, which notably is the site of ongoing keratinocyte DNA replication. Clearly, variations in product composition, nitrosamine metabolism, and exposure duration will modulate clinical outcomes. The data presented here form a coherent picture consistent with the abundant experimental data that link tobacco-specific nitrosamines to human oral cancer. PMID:24265177

  5. Renal Tumors in 26-Week Tg.Rash2 Mice Carcinogenicity Studies.

    PubMed

    Paranjpe, Madhav G; Belich, Jessica L; McKeon, Marie E; Elbekai, Reem H; Mann, Peter C; Hard, Gordon C; Seely, John C

    2016-07-01

    We report renal tubular adenomas and a carcinoma in 26-week Tg.rasH2 mouse carcinogenicity studies, which have not been reported to date either at our facility or in other published data. However, during the year 2014, renal tubular tumors were present in 4 studies conducted at our facility. Because of their morphological similarity to the amphophilic-vacuolar (AV) phenotypic variant of renal tubule tumors noted in Sprague-Dawley and Fischer 344 rats, which are thought to be familial, as well as the genetic homogeneity of Tg.rasH2 mice, we tracked the parents of these mice with tumors in each study. The origin of these tumors could not be traced back to any of the parents or even an animal barrier, and these tumors were not attributed to the vehicle or test article. Although the exact mechanism of tumorigenesis was not known, based on the available information, the development of renal tumors in these mice was considered random and spontaneous. PMID:26883151

  6. Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies

    PubMed Central

    Licht, Christoph; Greenbaum, Larry A; Muus, Petra; Babu, Sunil; Bedrosian, Camille L; Cohen, David J; Delmas, Yahsou; Douglas, Kenneth; Furman, Richard R; Gaber, Osama A; Goodship, Timothy; Herthelius, Maria; Hourmant, Maryvonne; Legendre, Christophe M; Remuzzi, Giuseppe; Sheerin, Neil; Trivelli, Antonella; Loirat, Chantal

    2015-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, possibly life-threatening disease characterized by platelet activation, hemolysis and thrombotic microangiopathy (TMA) leading to renal and other end-organ damage. We originally conducted two phase 2 studies (26 weeks and 1 year) evaluating eculizumab, a terminal complement inhibitor, in patients with progressing TMA (trial 1) and those with long duration of aHUS and chronic kidney disease (trial 2). The current analysis assessed outcomes after 2 years (median eculizumab exposure 100 and 114 weeks, respectively). At all scheduled time points, eculizumab inhibited terminal complement activity. In trial 1 with 17 patients, the platelet count was significantly improved from baseline, and hematologic normalization was achieved in 13 patients at week 26, and in 15 patients at both 1 and 2 years. The estimated glomerular filtration rate (eGFR) was significantly improved compared with baseline and year 1. In trial 2 with 20 patients, TMA event-free status was achieved by 16 patients at week 26, 17 patients at year 1, and 19 patients at year 2. Criteria for hematologic normalization were met by 18 patients at each time point. Improvement of 15 ml/min per 1.73 m2 or more in eGFR was achieved by 1 patient at week 26, 3 patients at 1 year, and 8 patients at 2 years. The mean change in eGFR was not significant compared with baseline, week 26, or year 1. Eculizumab was well tolerated, with no new safety concerns or meningococcal infections. Thus, a 2-year analysis found that the earlier clinical benefits achieved by eculizumab treatment of aHUS were maintained at 2 years of follow-up. PMID:25651368

  7. Treatment Compliance of Adolescents after Attempted Suicide: A 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    Burns, Craig D.; Cortell, Ranon; Wagner, Barry M.

    2008-01-01

    The study investigates compliance with mental health treatments among suicidal adolescents. Results show that child psychopathology and parental attitudes toward treatment plays an important part in increasing compliance with mental health treatment for adolescent suicide attempters.

  8. Carcinogenesis studies in rodents for evaluating risks associated with chemical carcinogens in aquatic food animals.

    PubMed Central

    Huff, J; Bucher, J; Yang, R

    1991-01-01

    Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver lesions. Long-term chemical carcinogenesis studies could be easily and feasibly designed using laboratory rodents offered diets containing fish caught in polluted waters. Induced cancers in rodents would corroborate field observations in fish; positive results from these studies would provide further evidence about potential human health hazards from eating substantial amounts of chemically contaminated fish. Nonetheless, fish and aquatic organisms should be viewed as environmental biological monitors of pollution or of potential human health hazards, and authorities responsible for assuring clean and safe rivers, bodies of water, and biota should give more attention to these valid biological indicators or sentinels of environmental pollution. Consequently, fish and other sea creatures alone should serve as alarms regarding whether water areas constitute public health hazards. PMID:2050050

  9. Carcinogenesis studies in rodents for evaluating risks associated with chemical carcinogens in aquatic food animals

    SciTech Connect

    Huff, J.; Bucher, J.; Yang, R. )

    1991-01-01

    Fish and shellfish caught in polluted waters contain potentially dangerous amounts of toxic and carcinogenic chemicals. Public concern was heightened when a large percentage of winter flounder taken from Boston Harbor was found to have visible cancer of the liver; winter flounder outside the estuary area had no liver lesions. Long-term chemical carcinogenesis studies could be easily and feasibly designed using laboratory rodents offered diets containing fish caught in polluted waters. Induced cancers in rodents would corroborate field observations in fish; positive results from these studies would provide further evidence about potential human health hazards from eating substantial amounts of chemically contaminated fish. Nonetheless, fish and aquatic organisms should be viewed as environmental biological monitors of pollution or of potential human health hazards, and authorities responsible for assuring clean and safe rivers, bodies of water, and biota should give more attention to these valid biological indicators or sentinels of environmental pollution. Consequently, fish and other sea creatures alone should serve as alarms regarding whether water areas constitute public health hazards. 101 refs.

  10. The toxic effects of flame retardants: a gene expression study in elucidating their carcinogenicity

    NASA Astrophysics Data System (ADS)

    Vagula, Mary; Al-Dhumani, Ali; Al-Dhumani, Sajaad; Mastro, Alexandra

    2013-05-01

    Polybrominated Diphenyl Ethers (PBDEs) are flame retardants widely used in many commercial products, including building materials, electronics, furnishings, motor vehicles, airplanes, plastics, polyurethane foams, and textiles. Although the specific toxic action of these chemicals is not clear, it is reported that they can cause serious damage to the nervous, reproductive, and endocrine systems. These chemicals are branded as "probable carcinogens" by Environmental Protection Agency (EPA). Therefore, this study is taken up to investigate the expression of genes namely, TP-53, RAD1, CRADD, and ATM, which are involved in apoptosis, DNA repair and cell cycle regulation. For this study human umbilical vein endothelial cells (HUVEC) are exposed to 5 μM of BDE-85 (a penta-BDE) and BDE-209 (deca-BDE). The results of this report reveal significant alteration in all the genes under investigation in BDE-85 and BDE-209 exposed cells. The BDE-85 induced responses are significantly more than BDE-209. These results emphasize the congener specific action of PBDEs on the expression of genes relevant to DNA repair and cell division of HUVEC cells.

  11. Diagnosis of Autism Spectrum Disorders in 2-Year-Olds: A Study of Community Practice

    ERIC Educational Resources Information Center

    Corsello, Christina M.; Akshoomoff, Natacha; Stahmer, Aubyn C.

    2013-01-01

    Background: Longitudinal research studies have demonstrated that experienced clinicians using standardized assessment measures can make a reliable diagnosis of autism spectrum disorders (ASDs) in children under age 3. Limited data are available regarding the sensitivity and specificity of these measures in community settings. The aims of this…

  12. Development of Orthographic Knowledge in German-Speaking Children: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Ise, Elena; Arnoldi, Carolin Judith; Schulte-Körne, Gerd

    2014-01-01

    There is growing evidence that children develop orthographic knowledge from the very beginning of literacy acquisition. This study investigated the development of German-speaking children's orthographic knowledge with a nonword choice task. One nonword in each pair contained a frequent consonant doublet ("zommul") and the other…

  13. Pubertal Timing and Substance Use in Middle Adolescence: A 2-Year Follow-Up Study

    ERIC Educational Resources Information Center

    Kaltiala-Heino, Riittakerttu; Koivisto, Anna-Maija; Marttunen, Mauri; Frojd, Sari

    2011-01-01

    Earlier research has associated early puberty with emotional and behavioral symptoms particularly among girls, while among boys, findings have been contradictory as to whether risks are associated with early or late pubertal timing. We studied the association between pubertal timing and substance use behaviors in middle adolescence in a 2-year…

  14. The Development of Falling Intonation in Young Children with Cochlear Implants: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Snow, David P.; Ertmer, David J.

    2013-01-01

    This article describes the development of intonation in 12 cochlear implant (CI) recipients. In a previously reported study of the first year of CI use, children who were implanted late (after 24 months) acquired intonation more rapidly than the younger participants. The older children's advantage is plausibly owing to their greater maturity.…

  15. A 2 year longitudinal study of Cryptosporidium species and genotypes in dairy cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this, the first long term longitudinal study of cryptosporidiosis in cattle, 30 pure-bred Holstein female cattle on a dairy farm in Maryland were examined consecutively at weekly, biweekly, or monthly intervals from 1 week to 24 months of age for the presence of Cryptosporidium oocysts. Feces wer...

  16. Predicting Expressive Vocabulary Acquisition in Children with Intellectual Disabilities: A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Vandereet, Joke; Maes, Bea; Lembrechts, Dirk; Zink, Inge

    2010-01-01

    Purpose: This study's objectives were to describe expressive vocabulary acquisition in children with intellectual disabilities (ID) and to examine specific pre- and early linguistic behaviors used to request and comment, chronological age, cognitive skills, and vocabulary comprehension as predictors of expressive vocabulary. Method: This study…

  17. Re-defining one's occupational self 2 years after breast cancer: a case study.

    PubMed

    Newman, Robin M

    2013-01-01

    Margaret*, a 56 year-old Caucasian Stage III breast cancer survivor, participated in a 5 week occupational therapy pilot program, called Take Action. This program was designed for breast cancer survivors who self-reported changes in cognitive function following completion of chemotherapy. The goals of the program were to improve participants' knowledge and use of strategies to enhance occupational performance and to improve satisfaction and performance of meaningful daily activities or occupations. Through a client-centered and evidence-based approach, this case study highlights the importance of incorporating the survivors' sense of self into an occupation-based intervention. Occupational therapists play an important role in facilitating exploration of sense of self in the survivorship phase of care to support occupational performance in self care, productivity, work, leisure and social participation. This case study highlights the important work of redefining oneself in the survivorship phase of care. (*denotes name change). PMID:24004739

  18. Molecular epidemiology studies on occupational and environmental exposure to mutagens and carcinogens, 1997-1999.

    PubMed Central

    Srám, R J; Binková, B

    2000-01-01

    Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure--metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect--chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility--genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens. PMID:10698723

  19. Studies on Carcinogenic and Toxic Effects of Ochratoxin A in Chicks

    PubMed Central

    Stoev, Stoycho D.

    2010-01-01

    Carcinogenic/toxic effects of ochratoxin A (OTA) in various internal organs of Plymouth Rock chicks were determined. The number of OTA-induced neoplasms was similar in chicks given 25 ppm L-β-phenylalanine (PHE) in addition to 5 ppm OTA compared to chicks given only 5 ppm OTA, which showed that PHE cannot be used as a real protector against the carcinogenic or toxic effects of OTA in chicks. OTA was found to provoke strong degenerative changes in liver and kidneys, degenerative changes and depletion of cells in lymphoid organs, oedematous and degenerative changes in the brain, muscular haemorrhages and fatty changes in the bone marrow. The target organs for carcinogenic effect of OTA in chicks were found to be kidneys and liver. PMID:22069604

  20. Acinetobacter Infections among Adult Patients in Qatar: A 2-Year Hospital-Based Study

    PubMed Central

    Al Samawi, Musaed Saad; Khan, Fahmi Yousef; Eldeeb, Yasser; Almaslamani, Muna; Alkhal, Abdullatif; Alsoub, Hussam; Ghadban, Wissam; Howady, Faraj; Hashim, Samar

    2016-01-01

    This retrospective study was conducted at Hamad General Hospital, Qatar, to describe the demographic data, clinical features underlying diseases, antimicrobial susceptibility, and outcome of A. baumannii infection. It involved all adult patients 15 years of age or older who were managed at Hamad General Hospital for A. baumannii infection from January 1, 2012, to December 31, 2013. We identified a total of 239 patients with A. baumannii infection, of which 182 (76.2%) were males. The mean age was 49.10 ± 19.57 years. The majority of the episodes (25.1%) occurred in elderly patients (≥65 years) and the most commonly identified site of A. baumannii infection was the respiratory tract, 117 (48.9%). Most episodes of infection, 231 (96.7%), were hospital-acquired and high rate of nosocomial infections occurred in the medical intensive care unit, 66 (28.6%). All patients had underlying medical conditions. Maximum resistance was seen to cefotaxime, 147 (58.3%), and minimum resistance was seen to colistin, 2 (1.4%). Of the 239 isolates, 102 (42.7%) were susceptible and 137 (57.3%) were multidrug-resistant. The in-hospital mortality in our study was 31%. Male gender, multidrug resistance, and septic shock were found to be independent mortality predictors. PMID:27433169

  1. Acinetobacter Infections among Adult Patients in Qatar: A 2-Year Hospital-Based Study.

    PubMed

    Al Samawi, Musaed Saad; Khan, Fahmi Yousef; Eldeeb, Yasser; Almaslamani, Muna; Alkhal, Abdullatif; Alsoub, Hussam; Ghadban, Wissam; Howady, Faraj; Hashim, Samar

    2016-01-01

    This retrospective study was conducted at Hamad General Hospital, Qatar, to describe the demographic data, clinical features underlying diseases, antimicrobial susceptibility, and outcome of A. baumannii infection. It involved all adult patients 15 years of age or older who were managed at Hamad General Hospital for A. baumannii infection from January 1, 2012, to December 31, 2013. We identified a total of 239 patients with A. baumannii infection, of which 182 (76.2%) were males. The mean age was 49.10 ± 19.57 years. The majority of the episodes (25.1%) occurred in elderly patients (≥65 years) and the most commonly identified site of A. baumannii infection was the respiratory tract, 117 (48.9%). Most episodes of infection, 231 (96.7%), were hospital-acquired and high rate of nosocomial infections occurred in the medical intensive care unit, 66 (28.6%). All patients had underlying medical conditions. Maximum resistance was seen to cefotaxime, 147 (58.3%), and minimum resistance was seen to colistin, 2 (1.4%). Of the 239 isolates, 102 (42.7%) were susceptible and 137 (57.3%) were multidrug-resistant. The in-hospital mortality in our study was 31%. Male gender, multidrug resistance, and septic shock were found to be independent mortality predictors. PMID:27433169

  2. Involvement in bullying and suicidal ideation in middle adolescence: a 2-year follow-up study.

    PubMed

    Heikkilä, Hanna-Kaisa; Väänänen, Juha; Helminen, Mika; Fröjd, Sari; Marttunen, Mauri; Kaltiala-Heino, Riittakerttu

    2013-02-01

    The objective of the study was to ascertain whether involvement in bullying increases the risk for subsequent suicidal ideation. A total of 2,070 Finnish girls and boys aged 15 were surveyed in the ninth grade (age 15) in schools, and followed up 2 years later in the Adolescent Mental Health Cohort Study. Involvement in bullying was elicited at age 15 by two questions focusing on being a bully and being a victim of bullying. Suicidal ideation was elicited by one item of the short Beck Depression Inventory at age 17. Baseline depressive symptoms and externalizing symptoms, age and sex were controlled for. Statistical analyses were carried out using cross-tabulations with Chi-square/Fisher's exact test and logistic regression. Suicidal ideation at age 17 was 3-4 times more prevalent among those who had been involved in bullying at age 15 than among those not involved. Suicidal ideation at age 17 was most prevalent among former victims of bullying. Being a victim of bullying at age 15 continued to predict subsequent suicidal ideation when depressive and externalizing symptoms were controlled for. Being a bully at age 15 also persisted as borderline significantly predictive of suicidal ideation when baseline symptoms were controlled for. Findings indicate adolescent victims and perpetrators of bullying alike are at long-term risk for suicidal ideation. PMID:23053774

  3. Prehospital versus Emergency Room Intubation of Trauma Patients in Qatar: A-2-year Observational Study

    PubMed Central

    Al-Thani, Hassan; El-Menyar, Ayman; Latifi, Rifat

    2014-01-01

    Background: The impact of prehospital intubation (PHI) in improving outcome of trauma patients has not been adequately evaluated in the developing countries. Aims: The present study analyzed the outcome of PHI versus emergency room intubation (ERI) among trauma patients in Qatar. Materials and Methods: Data were retrospectively reviewed for all intubated trauma patients between 2010 and 2011. Patients were classified according to location of intubation (PHI: Group-1 versus ERI: Group-2). Data were analyzed and compared. Results: Out of 570 intubated patients; 482 patients (239 in group-1 and 243 in group-2) met the inclusion criteria with a mean age of 32 ΁ 14.6 years Head injury (P = 0.003) and multiple trauma (P = 0.004) were more prevalent in group-1, whereas solid organ injury predominated in group-2 (P = 0.02). Group-1 had significantly higher mean injury severity scoring (ISS), lower Glasgow coma scale (GCS), greater head abbreviated injury score and longer activation, response, scene and total emergency medical services times. The mortality was higher in group-1 (53% vs. 18.5%; P = 0.001). Multivariate analysis showed that GCS [odds ratio (OR) 0.78, P = 0.005) and ISS (OR 1.12, P = 0.001) were independent predictors of mortality. Conclusions: PHI is associated with high mortality when compared with ERI. However, selection bias cannot be ruled out and therefore, PHI needs further critical assessment in Qatar. PMID:24678471

  4. A longitudinal study of cryptosporidiosis in dairy cattle from birth to 2 years of age.

    PubMed

    Santín, Mónica; Trout, James M; Fayer, Ronald

    2008-08-01

    Fecal specimens were collected from 30 calves from birth to 24 months of age at a dairy farm in Maryland to determine the prevalence and age distribution of Cryptosporidium species/genotypes. After centrifugation to remove debris and concentrate oocysts, specimens were examined by immunofluorescence microscopy and polymerase chain reaction (PCR). Fragments of the SSU-rDNA gene amplified by PCR were purified and PCR products were sequenced. All 30 calves shed Cryptosporidium oocysts at some time during the 24 months of the study. Of 990 specimens, 190 were Cryptosporidium-positive (19.2%). The highest prevalence of infection was at 2 weeks of age when 29 of the 30 calves were excreting oocysts. Prevalence was higher in pre-weaned calves (1-8 weeks of age) (45.8%) than in post-weaned calves (3-12 months of age) (18.5%) and heifers (12-24 months of age) (2.2%). Sequence data for 190 PCR-positive specimens identified: C. parvum, C. bovis, the Cryptosporidium deer-like genotype and C. andersoni, with cumulative prevalences of 100, 80, 60, and 3.3%, respectively. C. parvum constituted 97% of infections in pre-weaned calves but only 4% and 0% of infections in post-weaned calves and heifers, respectively. All C. parvum GP60 nucleotide sequences were subtype IIaA15G2R1. PMID:18565677

  5. Novel Transgenic Mouse Model for Studying Human Serum Albumin as a Biomarker of Carcinogenic Exposure.

    PubMed

    Sheng, Jonathan; Wang, Yi; Turesky, Robert J; Kluetzman, Kerri; Zhang, Qing-Yu; Ding, Xinxin

    2016-05-16

    Albumin is a commonly used serum protein for studying human exposure to xenobiotic compounds, including therapeutics and environmental pollutants. Often, the reactivity of albumin with xenobiotic compounds is studied ex vivo with human albumin or plasma/serum samples. Some studies have characterized the reactivity of albumin with chemicals in rodent models; however, differences between the orthologous peptide sequences of human and rodent albumins can result in the formation of different types of chemical-protein adducts with different interaction sites or peptide sequences. Our goal is to generate a human albumin transgenic mouse model that can be used to establish human protein biomarkers of exposure to hazardous xenobiotics for human risk assessment via animal studies. We have developed a human albumin transgenic mouse model and characterized the genotype and phenotype of the transgenic mice. The presence of the human albumin gene in the genome of the model mouse was confirmed by genomic PCR analysis, whereas liver-specific expression of the transgenic human albumin mRNA was validated by RT-PCR analysis. Further immunoblot and mass spectrometry analyses indicated that the transgenic human albumin protein is a full-length, mature protein, which is less abundant than the endogenous mouse albumin that coexists in the serum of the transgenic mouse. The transgenic protein was able to form ex vivo adducts with a genotoxic metabolite of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a procarcinogenic heterocyclic aromatic amine formed in cooked meat. This novel human albumin transgenic mouse model will facilitate the development and validation of albumin-carcinogen adducts as biomarkers of xenobiotic exposure and/or toxicity in humans. PMID:27028147

  6. Frequency and nature of spontaneous age-related eye lesions observed in a 2-year inhalation toxicity study in rats.

    PubMed

    Wegener, A; Kaegler, M; Stinn, W

    2002-01-01

    A group of 160 Wistar rats (both sexes) from a larger chronic inhalation toxicity study was monitored at baseline and after 1 and 2 years with a photo-slitlamp microscope and a direct ophthalmoscope to record spontaneous age-related eye lesions and treatment-related eye lesions over a period of 24 months. A second group from the same study was monitored at the start and after 5 months of a 6-month posttreatment period immediately following the inhalation period. Rats were nose-only exposed for 6 h/day, 7 days/week, for 2 years to low (3 microg/l) or high (10 microg/l) total particulate matter concentrations of room-aged cigarette sidestream smoke (RASS) or diesel engine exhaust (DEE). Control animals were exposed to filtered fresh air. All ophthalmological examinations were performed in mydriasis, and relevant observations were documented on color slide film. At baseline, all animals with eye lesions were excluded from the study. After 1 year, only minor lesions were found: retrolental opacities (14%) and a few cases of corneal dryness with reddish lid margins. After 2 years, 23% of the animals had unilateral or bilateral retrolental opacities, but the most frequent eye lesions were posterior subcapsular cataracts (PSC, 32%). Water clefts and spokes were found in 11% of the lenses and mature cataracts in 6%. All other eye lesions observed were much less frequent. There were a few cases of glaucoma, corneal dryness and stromal neovascularization. The frequency and type of lesion in animals monitored from the start of the posttreatment period was comparable to what was seen after 2 years. Toward the end of this period the frequency of mature cataracts went up to 9% and that of (secondary) glaucomas to 5%. None of the eye lesions observed showed any association in frequency or severity of expression to the treatment, either RASS or DEE, or to the sex of the animals. In comparison to the (limited) literature data available, far fewer corneal lesions were found in this

  7. Do cage effects influence tumor incidence? An examination of laboratory animal carcinogenicity studies utilizing Fischer 344 rats.

    PubMed

    Haseman, J K

    1988-08-01

    Approximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically-related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P less than 0.05 or P less than 0.01) effects were consistent with the number expected by chance alone. Thus, cage-related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current studies. PMID:3183292

  8. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF CYCLOPHOSPHAMIDE

    EPA Science Inventory

    Cyclophosphamide is a probable human carcinogen, classified as weight-of-evidence Group B1 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a).Evidence on potential carcinogenicity from animal studies is "Sufficient," and the evidence from human studies is "...

  9. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF DAUNOMYCIN

    EPA Science Inventory

    Daunomycin is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient," and the evidence from human studies is "No Dat...

  10. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF HYDRAZINE

    EPA Science Inventory

    Hydrazine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "sufficient," and the evidence from human studies is "Inadequ...

  11. A critical assessment of studies on the carcinogenic potential of diesel exhaust.

    PubMed

    Hesterberg, Thomas W; Bunn, William B; Chase, Gerald R; Valberg, Peter A; Slavin, Thomas J; Lapin, Charles A; Hart, Georgia A

    2006-10-01

    After decades of research involving numerous epidemiologic studies and extensive investigations in laboratory animals, a causal relationship between diesel exhaust (DE) exposure and lung cancer has not been conclusively demonstrated. Epidemiologic studies of the transportation industry (trucking, busing, and railroad) show a small elevation in lung cancer incidence (relative risks [RRs] generally below 1.5), but a dose response for DE is lacking. The studies are also limited by a lack of quantitative concurrent exposure data and inadequate or lack of controls for potential confounders, particularly tobacco smoking. Furthermore, prior to dieselization, similar elevations in lung cancer incidence have been reported for truck drivers, and in-cab diesel particulate matter (DPM) exposures of truck drivers were comparable to ambient highway exposures. Taken together, these findings suggest that an unidentified occupational agent or lifestyle factor might be responsible for the low elevations in lung cancer reported in the transportation studies. In contrast, underground miners, many of whom experience the highest occupational DPM exposures, generally do not show elevations in lung cancer. Laboratory studies must be interpreted with caution with respect to predicting the carcinogenic potential of DE in humans. Tumors observed in rats following lifetime chronic inhalation of very high levels of DPM may be attributed to species-specific overload mechanisms that lack relevance to humans. Increased tumor incidence was not observed in other species (hamsters or mice) exposed to DPM at very high levels or in rats exposed at lower levels (studies in which cells were exposed to concentrated extracts of DPM also have limited application to human risk assessment, because such extracts can be obtained from DPM only by using strong organic solvents, agitation, and heat. Most studies have shown that whole DPM itself is not

  12. Toxicity and Carcinogenicity Studies of Ginkgo biloba extract in Rat and Mouse: Liver, Thyroid, and Nose are Targets

    PubMed Central

    Rider, Cynthia V.; Nyska, Abraham; Cora, Michelle C.; Kissling, Grace E.; Smith, Cynthia; Travlos, Gregory S.; Hejtmancik, Milton R.; Fomby, Laurene M.; Colleton, Curtis A.; Ryan, Michael J.; Kooistra, Linda; Morrison, James P.; Chan, Po C.

    2014-01-01

    Ginkgo biloba extract (GBE) is a popular herbal supplement that is used to improve circulation and brain function. In spite of widespread human exposure to relatively high doses over potentially long periods of time, there is a paucity of data from animal studies regarding the toxicity and carcinogenicity associated with GBE. In order to fill this knowledge gap, three-month and two-year toxicity and carcinogenicity studies with GBE administered by oral gavage to B6C3F1/N mice and F344/N rats were performed as part of the National Toxicology Program’s Dietary Supplements and Herbal Medicines Initiative. The targets of GBE treatment were the liver, thyroid, and nose. These targets were consistent across exposure period, sex, and species, albeit with varying degrees of effect observed among studies. Key findings included a notably high incidence of hepatoblastomas in male and female mice and evidence of carcinogenic potential in the thyroid gland of both mice and rats. Various nonneoplastic lesions were observed beyond control levels in the liver, thyroid gland, and nose of rats and mice administered GBE. Although these results cannot be directly extrapolated to humans, the findings fill an important data gap in assessing risk associated with GBE use. PMID:23960164

  13. Talent identification and early development of elite water-polo players: a 2-year follow-up study.

    PubMed

    Falk, Bareket; Lidor, Ronnie; Lander, Yael; Lang, Benny

    2004-04-01

    The processes of talent detection and early development are critical in any sport programme. However, not much is known about the appropriate strategies to be implemented during these processes, and little scientific inquiry has been conducted in this area. The aim of this study was to identify variables of swimming, ball handling and physical ability, as well as game intelligence, which could assist in the selection process of young water-polo players. Twenty-four players aged 14-15 years underwent a battery of tests three times during a 2-year period, before selection to the junior national team. The tests included: freestyle swim for 50, 100, 200 and 400 m, 100-m breast-stroke, 100-m 'butterfly' (with breast-stroke leg motion), 50-m dribbling, throwing at the goal, throw for distance in the water, vertical 'jump' from the water, and evaluation of game intelligence by two coaches. A comparison of those players eventually selected to the team and those not selected demonstrated that, 2 years before selection, selected players were already superior on most of the swim tasks (with the exception of breast-stroke and 50-m freestyle), as well as dribbling and game intelligence. This superiority was maintained throughout the 2 years. Two-way tabulation revealed that, based on baseline scores, the prediction for 67% of the players was in agreement with the final selection to the junior national team. We recommend that fewer swim events be used in the process of selecting young water-polo players, and that greater emphasis should be placed on evaluation of game intelligence. PMID:15161108

  14. Evaluation of potential activity of luseogliflozin on vascular proliferation in the mesenteric lymph node with or without vascular tumors in Sprague-Dawley rats in a carcinogenicity study

    PubMed Central

    Sasaki, Minoru; Sakurai, Takanobu; Ishii, Aiko; Matsue, Kenta; Nakanishi, Yutaka; Tsutsumi, Shunsuke; Sato, Yasushi

    2016-01-01

    The incidence of mesenteric lymph node vascular tumors can vary in rats, and appropriate assessment of potential risk of tumorigenicity is needed when the incidence is higher in treated groups than in a control group. In a 2-year rat carcinogenicity study of luseogliflozin, a selective sodium-dependent glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus, there was a slight but statistically significant increase in the total number of hemangiomas and hemangiosarcomas in the mesenteric lymph nodes in males at a high-dose. As part of the risk assessment for luseogliflozin, its effect on the vascular proliferation potential in the mesenteric lymph nodes was examined in a rat carcinogenicity study by performing an image analysis using specimens with double immunohistochemical staining for PCNA and CD34 in control and high-dose males. In addition, immunohistochemical staining for VEGF was performed to detect enhanced angiogenesis. In the high-dose males that did not have a hemangioma/hemangiosarcoma, neither an increased number of PCNA/CD34-positive cells nor changes in the expression pattern of VEGF was observed. On the other hand, in the high-dose males that had a hemangioma/hemangiosarcoma, the number of PCNA-positive cells was increased in the tumor areas, and the number in the hemangioma/hemangiosarcoma was approximately one-half of that in the hemangiosarcoma in the control male. In conclusion, no potential change leading to vascular proliferation/tumors was detected in the mesenteric lymph nodes of high-dose males receiving luseogliflozin. PMID:27182112

  15. Carcinogenicity studies on natural and man-made fibres with the intraperitoneal test in rats.

    PubMed

    Pott, F; Roller, M; Ziem, U; Reiffer, F J; Bellmann, B; Rosenbruch, M; Huth, F

    1989-01-01

    Female Wistar rats were injected intraperitoneally (i.p.) with a suspension of 11 fibrous and 3 granular dusts. A dose of 0.25 mg actinolite or UICC chrysotile induced tumours of the peritoneum in more than 50% of the animals. Even 0.05 and 0.01 mg proved to be carcinogenic, although no adhesions of the abdominal organs could be observed. The findings are in conflict with the hypothesis that a scar is always the morphological precondition for the development of an asbestos-induced tumour. Actinolite injected i.p. in a solution of polyvinylpyridine-N-oxide gave a lower tumour incidence than when suspended only in saline, possibly due to inactivation of the fibre surface. Persistent glass fibres were less effective than actinolite having a similar fibre size distribution. On the other hand, relatively thick basalt fibres and ceramic fibres gave higher tumour incidences than expected. Wollastonite fibres were not carcinogenic, probably because of their low durability. Large amounts of polyvinylchloride, alpha-ferric oxide hydrate and wood dust also led only to adhesions of the abdominal organs and fibrosis; a definite carcinogenic effect was not detected. PMID:2744824

  16. Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US

    PubMed Central

    Adams, Edgar H; McElroy, Heather J; Udall, Margarita; Masters, Elizabeth T; Mann, Rachael M; Schaefer, Caroline P; Cappelleri, Joseph C; Clair, Andrew G; Hopps, Markay; Daniel, Shoshana R; Mease, Philip; Silverman, Stuart L; Staud, Roland

    2016-01-01

    Background A previous fibromyalgia (FM) research reports that 20%–47% of diagnosed patients may not meet the study definition of FM 1–2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. Methods This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM−CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM−CWP− (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. Results Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM−CWP− and nine became FM−CWP+). Ten subjects (two from FM−CWP− and eight from FM−CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. Conclusion The results suggest that some FM+CWP+ patients experience

  17. Natural carcinogenic fiber and pleural plaques assessment in a general population: A cross-sectional study.

    PubMed

    Ledda, Caterina; Pomara, Cristoforo; Bracci, Massimo; Mangano, Dario; Ricceri, Vincenzo; Musumeci, Andrea; Ferrante, Margherita; Musumeci, Giuseppe; Loreto, Carla; Fenga, Concettina; Santarelli, Lory; Rapisarda, Venerando

    2016-10-01

    Natural carcinogenic fibers are asbestos and asbestiform fibers present as a natural component of soils or rocks. These fibers are released into the environment resulting in exposure of the general population. Environmental contamination by fibers are those cases occurred in: rural regions of Turkey, in Mediterranean countries and in other sites of the world, including northern Europe, USA and China. Fluoro-edenite(FE) is a natural mineral species first isolated in Biancavilla, Sicily. The fibers are similar in size and morphology to some amphibolic asbestos fibers, whose inhalation can cause chronic inflammation and cancer. The aim of the current study is to assess the presence and features of pleural plaques (PPs) in Biancavilla's general population exposed to FE through a retrospective cross-sectional study. All High-Resolution Computed Tomography (HRCT) chest scans carried out between June 2009 and June 2015 in Biancavilla municipality hospital site (exposed subjects) were reviewed. The exposed groups were 1:1 subjects, matched according to age and sex distributions, with unexposed subjects (n.1.240) randomly selected among HRCT chest scans carried out in a Hospital 30km away from Biancavilla. Subjects from Biancavilla with PPs were significantly more numerous than the control group ones (218 vs 38). Average age of either group was >60 years; the age of exposed subjects was significantly (p=0.0312) lesser than the unexposed group. In exposed subjects, in most PPs thickness ranged between 2 and 4.9cm(38%, n=83); while in unexposed ones PPs thickness was less than 2cm (55%, n=21). As to the size of PPs in exposed subjects, in most cases it ranged between 1cm and 24% of chest wall (53%, n=116); while in unexposed ones the size of PPs was lesser than 1cm (23%, n=58). Among exposed subjects, 36 cases (17%) PPs were detected with calcification, whereas in unexposed ones only three (8%) presented calcification. 137 lung parenchymal abnormalities were observed in

  18. The role of transgenic mouse models in carcinogen identification.

    PubMed Central

    Pritchard, John B; French, John E; Davis, Barbara J; Haseman, Joseph K

    2003-01-01

    In this article, we examine existing data on the use of transgenic mouse models for identification of human carcinogens. We focus on the three most extensively studied of these mice, Trp53+/-, Tg/AC, and RasH2, and compare their performance with the traditional 2-year rodent bioassay. Data on 99 chemicals were evaluated. Using the International Agency for Research on Cancer/Report on Carcinogens determinations for the carcinogenicity of these chemicals to humans as the standard for comparison, we evaluated a variety of potential testing strategies ranging from individual transgenic models to combinations of these three models with each other and with traditional rodent assays. The individual transgenic models made the "correct" determinations (positive for carcinogens; negative for noncarcinogens) for 74-81% of the chemicals, with an increase to as much as 83% using combined strategies (e.g., Trp53+/- for genotoxic chemicals and RasH2 for all chemicals). For comparison, identical analysis of chemicals in this data set that were tested in the 2-year, two-species rodent bioassay yielded correct determinations for 69% of the chemicals. However, although the transgenic models had a high percentage of correct determinations, they did miss a number of known or probable human carcinogens, whereas the bioassay missed none of these chemicals. Therefore, we also evaluated mixed strategies using transgenic models and the rat bioassay. These strategies yielded approximately 85% correct determinations, missed no carcinogens, and cut the number of positive determinations for human noncarcinogens in half. Overall, the transgenic models performed well, but important issues of validation and standardization need further attention to permit their regulatory acceptance and use in human risk assessment. PMID:12676597

  19. Quality of life of breast cancer patients medicated with anti-estrogens, 2 years after acupuncture treatment: a qualitative study

    PubMed Central

    Hervik, Jill; Mjåland, Odd

    2010-01-01

    Objective The aim of this study was to examine the quality of life of breast cancer patients medicated with estrogen antagonists, 2 years after having acupuncture treatment for hot flashes. Methods and materials Our sample was taken from women who had recently participated in a randomized controlled trial investigating the effects of acupuncture on hot flashes, a side effect of estrogen-antagonist treatment. Forty-one women from the true acupuncture treatment group and 41 women from the control group (sham acupuncture), who had 2 years previously received a course of 15 acupuncture treatments over a period of 10 weeks, were asked to answer an open question. The question, “Would you like to share your thoughts and experiences related to your breast cancer diagnosis, treatments or anything else?” was by being open, broad, and nonspecific, intended to stimulate subjective information, which was not included in the original, or future quantitative studies. Qualitative data were analyzed using systematic text condensation. Results Most women were troubled by two or more side effects due to anti-estrogen medication, negatively affecting their life quality. Symptoms included hot flashes, sleep problems, muscle and joint pain, arm edema, fatigue, weight gain, depression, and lack of sexual desire. Women previously treated with sham acupuncture complained that hot flashes were still problematic, whilst those previously treated with traditional Chinese acupuncture found them less of a problem and generally had a more positive outlook on life. These results compare favorably with the findings from our original study that measured quantitatively health related quality of life. Conclusion Side effects due to anti-estrogen treatment seriously affect the quality of life of breast cancer operated patients. Patients who had previously been treated with traditional Chinese acupuncture complained less of hot flashes, and had a more positive outlook on life, than women who had

  20. Disordered eating behaviors and body image in a longitudinal pilot study of adolescent girls: what happens 2 years later?

    PubMed

    Espinoza, Paola; Penelo, Eva; Raich, Rosa M

    2010-01-01

    We assessed the prospective association of risk factors for eating and body image disturbances after a 2-year follow-up in a community sample of Spanish adolescent girls. The participants included 128 Spanish girls aged 12-14, who took part in a 28-month prospective study. Aspects assessed were eating attitudes (Eating Attitudes Test), influence of the body shape model (questionnaire on influences of the aesthetic body shape model), extreme weight-control behaviors (Eating Disorder Examination-Questionnaire), body image (Body Image Questionnaire) and Body Mass Index (BMI). BMI, extreme weight-control behaviors and body image problems emerged as potential predictors of an increase in eating disturbances. An increased influence of the thinness model was significantly associated with reduced body satisfaction and body image problems. Preventive programs are needed to contribute reducing the impact of sociocultural influences with regard to thinness, the use of extreme weight-control behaviors and overweight in adolescents. PMID:19815475

  1. The improving outcomes in intermittent exotropia study: outcomes at 2 years after diagnosis in an observational cohort

    PubMed Central

    2012-01-01

    Background The purpose of this study was to investigate current patterns of management and outcomes of intermittent distance exotropia [X(T)] in the UK. Methods This was an observational cohort study which recruited 460 children aged < 12 years with previously untreated X(T). Eligible subjects were enrolled from 26 UK hospital ophthalmology clinics between May 2005 and December 2006. Over a 2-year period of follow-up, clinical data were prospectively recorded at standard intervals from enrolment. Data collected included angle, near stereoacuity, visual acuity, control of X(T) measured with the Newcastle Control Score (NCS), and treatment. The main outcome measures were change in clinical outcomes (angle, stereoacuity, visual acuity and NCS) in treated and untreated X(T), 2 years from enrolment (or, where applicable, 6 months after surgery). Change over time was tested using the chi-square test for categorical, Wilcoxon test for non-parametric and paired-samples t-test for parametric data. Results At follow-up, data were available for 371 children (81% of the original cohort). Of these: 53% (195) had no treatment; 17% (63) had treatment for reduced visual acuity only (pure refractive error and amblyopia); 13% (50) had non surgical treatment for control (spectacle lenses, occlusion, prisms, exercises) and 17% (63) had surgery. Only 0.5% (2/371) children developed constant exotropia. The surgically treated group was the only group with clinically significant improvements in angle or NCS. However, 8% (5) of those treated surgically required second procedures for overcorrection within 6 months of the initial procedure and at 6-month follow-up 21% (13) were overcorrected. Conclusions Many children in the UK with X(T) receive active monitoring only. Deterioration to constant exotropia, with or without treatment, is rare. Surgery appears effective in improving angle of X(T) and NCS, but rates of overcorrection are high. PMID:22257496

  2. Prospective study of cognitive function in children receiving whole-brain radiotherapy and chemotherapy: 2-year results

    SciTech Connect

    Packer, R.J.; Sutton, L.N.; Atkins, T.E.; Radcliffe, J.; Bunin, G.R.; D'Angio, G.; Siegel, K.R.; Schut, L. )

    1989-05-01

    As survival rates have risen for children with malignant primary brain tumors, so has the concern that many survivors have significant permanent cognitive deficits. Cranial irradiation (CRT) has been implicated as the major cause for cognitive dysfunction. To clarify the etiology, incidence, and severity of intellectual compromise in children with brain tumors after CRT, a prospective study was undertaken comparing the neuropsychological outcome in 18 consecutive children with malignant brain tumors treated with CRT to outcome in 14 children harboring brain tumors in similar sites in the nervous system who had not received CRT. Children with cortical or subcortical brain tumors were not eligible for study. Neuropsychological testing was performed after surgery prior to radiotherapy, after radiotherapy, and at 1- and 2-year intervals thereafter. Children who had received CRT had a mean full-scale intelligence quotient (FSIQ) of 105 at diagnosis which fell to 91 by Year 2. Similar declines were noted in their performance intelligence quotient (IQ) and verbal IQ. After CRT, patients demonstrated a statistically significant decline from baseline in FSIQ (p less than 0.02) and verbal IQ (p less than 0.04). Children who had not received CRT did not demonstrate a fall in any cognitive parameter over time. The decline between baseline testing and testing performed at Year 2 in patients who had CRT was inversely correlated with age (p less than 0.02), as younger children demonstrated the greatest loss of intelligence. Children less than 7 years of age at diagnosis had a mean decline in FSIQ of 25 points 2 years posttreatment. No other clinical parameter correlated with the overall IQ or decline in IQ. After CRT, children demonstrated a wide range of dysfunction including deficits in fine motor, visual-motor, and visual-spatial skills and memory difficulties.

  3. Carcinogen risk assessment

    SciTech Connect

    Hazelwoold, R.N.

    1987-01-01

    This article describes the methods by which risk factors for carcinogenic hazards are determined and the limitations inherent in the process. From statistical and epidemiological studies, the major identifiable factors related to cancer in the United States were determined to be cigarette smoking, diet, reproductive and sexual behavior, infections, ultraviolet and ionizing radiation, and alcohol consumption. The incidence of lung cancer due to air pollutants was estimated to be less than 2%. Research needs were discussed.

  4. Use of Ergonomic Measures Related to Musculoskeletal Complaints among Construction Workers: A 2-year Follow-up Study

    PubMed Central

    Boschman, Julitta S.; Frings-Dresen, Monique H.W.; van der Molen, Henk F.

    2015-01-01

    Background The physical work demands of construction work can be reduced using ergonomic measures. The aim of this study was to evaluate the use of ergonomic measures related to musculoskeletal disorders (MSDs) among construction workers. Methods A questionnaire was sent at baseline and 2 years later to 1,130 construction workers. We established (1) the proportion of workers reporting an increase in their use of ergonomic measures, (2) the proportion of workers reporting a decrease in MSDs, (3) the relative risk for an increase in the use of ergonomic measures and a decrease in MSDs, and (4) workers' knowledge and opinions about the use of ergonomic measures. Results At follow-up, response rate was 63% (713/1,130). The proportion of workers using ergonomic measures for vertical transport increased (34%, 144/419, p < 0.01); for measures regarding horizontal transport and the positioning of materials, no change was reported. The proportion of workers reporting shoulder complaints decreased (28%, 176/638, p = 0.02). A relationship between the use of ergonomic measures and MSDs was not found; 83% (581/704) of the workers indicated having sufficient knowledge about ergonomic measures. Lightening the physical load was reported to be the main reason for using them. Conclusion Only the use of ergonomic measures for vertical transport increased over a 2-year period. No relationship between the use of ergonomic measures and MSDs was found. Strategies aimed at improving the availability of ergonomic equipment complemented with individualized advice and training in using them might be the required next steps to increase the use of ergonomic measures. PMID:26106507

  5. Lumbar total disc replacement using ProDisc II: a prospective study with a 2-year minimum follow-up.

    PubMed

    Chung, Sung Soo; Lee, Chong Suh; Kang, Chang Seok

    2006-08-01

    A lumbar total disc replacement (TDR) is believed to be a promising substitute in the surgical treatment for lumbar degenerative disc disease. The purpose of this study is to report the clinical and radiographic outcomes of 36 consecutive patients who underwent lumbar TDR using ProDisc II, and the factors associated with a better clinical outcome after a 2-year minimum follow-up. At the time of the latest follow-up, the success rate was 94% of 36 patients according to the criteria of the US Food and Drug Administration. Of the 10 patients unable to work preoperatively, 7 patients returned to work. Moreover, mean score on the visual analog scale for low back and leg pain improved significantly from 7.5 and 4.7 to 3.0 and 1.2, respectively (P<0.001). In addition, mean Oswestry disability index scores improved significantly from 69.2 to 21.0 (P<0.001). Mean disc height at the operative level increased significantly from 9.0 to 17.6 mm, and mean range of motion increased significantly from 9.7 to 12.7 degrees (P<0.01). Statistical analysis showed that the factors associated with a better clinical outcome were single level, and a higher postoperative segmental ROM at the operative level. At a minimum follow-up of 2 years, the lumbar TDR using ProDisc II showed excellent clinical and radiographic outcomes without any significant complication. However, future efforts need to be directed toward the evaluation of a larger number of patients with longer follow-up. PMID:16891976

  6. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study

    SciTech Connect

    Ruano-Ravina, Alberto; García-Lavandeira, José Antonio; Torres-Durán, María; Prini-Guadalupe, Luciana; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Montero-Martínez, Carmen; González-Barcala, Francisco Javier; Golpe-Gómez, Antonio; Martínez, Cristina; Castro-Añón, Olalla; Mejuto-Martí, María José; and others

    2014-07-15

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78–2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93–5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. - Highlights: • Some leisure time activities are associated with the exposure to carcinogenic substances. • These activities are model-making, painting (artistic or not), furniture refinishing or wood working. • Few studies have assessed lung cancer risk due to these hobbies and none in never-smokers. • Leisure activities related to exposure to carcinogenic substances present higher lung cancer risk. • The risk is higher when these activities are performed for more than 10 years.

  7. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice

    SciTech Connect

    Yokose, Y.; Uchida, K.; Nakae, D.; Shiraiwa, K.; Yamamoto, K.; Konishi, Y.

    1987-12-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentration of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice.

  8. Prevalidation study of the BALB/c 3T3 cell transformation assay for assessment of carcinogenic potential of chemicals.

    PubMed

    Tanaka, Noriho; Bohnenberger, Susanne; Kunkelmann, Thorsten; Munaro, Barbara; Ponti, Jessica; Poth, Albrecht; Sabbioni, Enrico; Sakai, Ayako; Salovaara, Susan; Sasaki, Kiyoshi; Thomas, B Claire; Umeda, Makoto

    2012-04-11

    The cell transformation assays (CTAs) have attracted attention within the field of alternative methods due to their potential to reduce the number of animal experiments in the field of carcinogenicity. The CTA using BALB/c 3T3 cells has proved to be able to respond to chemical carcinogens by inducing morphologically transformed foci. Although a considerable amount of data on the performance of the assay has been collected, a formal evaluation focusing particularly on reproducibility, and a standardised protocol were considered important. Therefore the European Centre for the Validation of Alternative Methods (ECVAM) decided to coordinate a prevalidation study of the BALB/c 3T3 CTA. Three different laboratories from Japan and Europe participated. In the study the following modules were assessed stepwise: test definition (Module 1) consisted of the standardisation of the protocol, the selection of the cell lineage, and the preparation of a photo catalogue on the transformed foci. The within-laboratory reproducibility (Module 2) and the transferability (Module 3) were assessed using non-coded and coded 3-methylcholanthrene. Then, five coded chemicals were tested for the assessment of between-laboratory reproducibility (Module 4). All three laboratories obtained positive results with benzo[a]pyrene, phenanthrene and o-toluidine HCl. 2-Acetylaminofluorene was positive in two laboratories and equivocal in one laboratory. Anthracene was negative in all three laboratories. The chemicals except phenanthrene, which is classified by IARC (http://monographs.iarc.fr) as group 3 "not classifiable as to its carcinogenicity to human", were correctly predicted as carcinogens. Further studies on phenanthrene will clarify this discrepancy. Thus, although only a few chemicals were tested, it can be seen that the predictive capacity of the BALB/c 3T3 CTA is satisfactory. On the basis of the outcome of this study, an improved protocol, incorporating some changes related to data

  9. Chronic dietary toxicity and carcinogenicity study with ammonium perfluorooctanoate in Sprague-Dawley rats.

    PubMed

    Butenhoff, John L; Kennedy, Gerald L; Chang, Shu-Ching; Olsen, Geary W

    2012-08-16

    In order to assess the potential chronic toxicity and tumorigenicity of ammonium perfluorooctanoate (APFO), a 2-year dietary study was conducted with male and female rats fed 30 ppm or 300 ppm (approximately 1.5 and 15 mg/kg). In males fed 300 ppm, mean body weights were lower across most of the test period and survival in these rats was greater than that seen either in the 30 ppm or the control group. Non-neoplastic effects were observed in liver in rats fed 300 ppm and included elevated liver weight, an increase in the incidence of diffuse hepatocellular hypertrophy, portal mononuclear cell infiltration, and mild hepatocellular vacuolation without an increase in hepatocellular necrosis. Mean serum activities of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were elevated up to three times the control means, primarily at the 300 ppm dose. A significant increase in Leydig cell tumors of the testes was seen in the males fed 300 ppm, and tumors of the liver and acinar pancreas, which are often observed in rats from chronic exposure to peroxisome proliferating agents, were not observed in this study. All other tumor types were those seen spontaneously in rats of this stock and age and were not associated with feeding of APFO. PMID:22531602

  10. Studies on the mutagenic mechanisms of the potent environmental carcinogen, benzo[a]pyrene

    SciTech Connect

    Rodriguez, H.

    1993-01-01

    Environmental chemicals that cause cancer have previously been shown to become chemically linked to the genetic substance, DNA, to give DNA adducts. These adducts appear foreign to the cell and mutations occur when the DNA is being duplicated during cell replication. Mutations in proto-oncogenes can change a normal cell into a cancerous cell. Benzo[a]pyrene is one example of a potent mutagen/carcinogen found ubiquitously in the environment: For example, in the soot from internal combustion engines and power plants, in cigarette smoke, and on charred meat. Benzo[a]pyrene is an indirect-acting mutagen/carcinogen, which must be metabolized inside the body to its ultimate mutagen/carcinogen, the corresponding (+)-anti-diol epoxide ((+)-anti-B[a]PDE) which forms many adducts in DNA. By using a newly developed forward mutation assay (ES87/pUB3) mutations induced by (+)-anti-B[a]PDE were isolated and characterized. SOS induction was shown to enhance frameshift and base pairing mutagenesis; G:C->T:A mutations were preferentially enhanced (approximately twelve-fold). Nearest neighbor analysis was performed assuming a guanine (underlined) was being mutated; SOS enhanced (+)-anti-B[a]PDE base pairing mutagenesis in 5[prime]-(A/T)G-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences, and in 5[prime]-G(C/G)-3[prime] sequences more than in 5[prime]-G(A/T)-3[prime] sequences. Sequence content affected mutagenesis quantitatively where hot-spots for (+)-anti-B[a]PDE was heated prior to transformation into ES87 cells, an approximately two-fold decrease in mutation frequency was observed. In general, heating did not affect mutagenic specificity. Models are proposed to explain these results. Freeze/thawing pUB3 adducted with (+)-anti-B[a]PDE, also caused both an approximately two-fold decrease in mutation frequency and changes similar to those caused by heating.

  11. Work–family conflict and health in Swedish working women and men: a 2-year prospective analysis (the SLOSH study)

    PubMed Central

    Baltzer, Maria; Magnusson Hanson, Linda L.; Westerlund, Hugo

    2013-01-01

    Background: Research has suggested that gender is related to perceptions of work–family conflict (WFC) and an underlying assumption is that interference of paid work with family life will burden women more than men. There is, however, mixed evidence as to whether men and women report different levels of WFC. Even less studies investigate gender differences in health outcomes of WFC. Also the number of longitudinal studies in this field is low. Methods: Based on the Swedish Longitudinal Occupational Survey of Health, we prospectively examined the effects of WFC on three different health measures representing a wide spectrum off ill health (i.e. self-rated health, emotional exhaustion and problem drinking). Logistic regression analyses were used to analyse multivariate associations between WFC in 2008 and health 2 years later. Results: The results show that WFC was associated with an increased risk of emotional exhaustion among both men and women. Gender differences are suggested as WFC was related to an increased risk for poor self-rated health among women and problem drinking among men. Interaction analyses revealed that the risk of poor self-rated health was substantially more influenced by WFC among women than among men. Conclusions: We conclude that, despite the fact that women experience conflict between work and family life slightly more often than men, both men’s and women’s health is negatively affected by this phenomenon. PMID:22683777

  12. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    PubMed Central

    Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-01-01

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate. PMID:24202448

  13. Controlled release study of an anti-carcinogenic agent, gallate from the surface of magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Ghotbi, Mohammad Yeganeh; bin Hussein, Mohd Zobir

    2012-07-01

    Immobilization of gallate anion, an anti-carcinogenic, anti-mutagenic, and anti-microbial agent on the surface of magnetite nanoparticles was accomplished by adsorption technique for the formation of a core-shell nanocomposite. A simple co-precipitation technique in the presence of poly vinyl pyrrolidone was successfully applied for the preparation of magnetite nanoparticles as core beads with narrow size distribution. The powders were characterized by X-ray diffraction, particle size analysis, magnetic measurements, atomic force microscope and also infrared spectroscopy. FTIR and CHNS results indicated that the gallate anion was actually adsorbed onto the surface of the magnetite nanoparticles. The release of the anion from the surface of the nanocomposite was found to be controllable by the selection of the release media.

  14. Breast cancer risk in relation to occupations with exposure to carcinogens and endocrine disruptors: a Canadian case–control study

    PubMed Central

    2012-01-01

    Background Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours. Methods 1005 breast cancer cases referred by a regional cancer center and 1146 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case–control design, exposure effects were estimated using conditional logistic regression. Results Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5). Conclusions These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and

  15. Carcinogenicity study of ammonia-process caramel in F344 rats.

    PubMed

    Maekawa, A; Ogiu, T; Matsuoka, C; Onodera, H; Furuta, K; Tanigawa, H; Hayashi, Y; Odashima, S

    1983-06-01

    The carcinogenicity of ammonia-process caramel, a food colouring, was examined in F344 rats. Caramel was dissolved in distilled water at levels of 0, 1 and 4% and groups of 50 male and 50 female rats were given 20-25 ml of one of these solutions/rat/day as their drinking water for 2 yr. There were no significant differences between the total incidences of tumours or mean survival times of control and experimental groups. A variety of tumours developed in all groups including the control group, and no dose-related effects were found either in the incidence or induction time of tumours in the various organs and tissues except in the pituitary gland of males, in which the incidence of tumours in males given 4% caramel solution was significantly higher than that in controls. Pituitary tumours are among the most common spontaneous tumours in ageing rats of this strain and have a variable incidence. In addition, almost all pituitary tumours detected in males given the 4% solution were microscopic tumours, and there was no significant difference between controls and treated groups in the incidence of hyperplasia or pre-neoplastic lesions in the pituitary gland. These results indicate that the significantly higher incidence of pituitary tumours in males given the 4% caramel solution was not related to caramel administration, but could be explained by the variability of the incidence of spontaneous pituitary tumours. Thus it is concluded that under these experimental conditions ammonia-process caramel was not carcinogenic in F344 rats. PMID:6683219

  16. Differences in predictors of traditional and cyber-bullying: a 2-year longitudinal study in Korean school children.

    PubMed

    Yang, Su-Jin; Stewart, Robert; Kim, Jae-Min; Kim, Sung-Wan; Shin, Il-Seon; Dewey, Michael E; Maskey, Sean; Yoon, Jin-Sang

    2013-05-01

    Traditional bullying has received considerable research but the emerging phenomenon of cyber-bullying much less so. Our study aims to investigate environmental and psychological factors associated with traditional and cyber-bullying. In a school-based 2-year prospective survey, information was collected on 1,344 children aged 10 including bullying behavior/experience, depression, anxiety, coping strategies, self-esteem, and psychopathology. Parents reported demographic data, general health, and attention-deficit hyperactivity disorder (ADHD) symptoms. These were investigated in relation to traditional and cyber-bullying perpetration and victimization at age 12. Male gender and depressive symptoms were associated with all types of bullying behavior and experience. Living with a single parent was associated with perpetration of traditional bullying while higher ADHD symptoms were associated with victimization from this. Lower academic achievement and lower self esteem were associated with cyber-bullying perpetration and victimization, and anxiety symptoms with cyber-bullying perpetration. After adjustment, previous bullying perpetration was associated with victimization from cyber-bullying but not other outcomes. Cyber-bullying has differences in predictors from traditional bullying and intervention programmes need to take these into consideration. PMID:23640732

  17. Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES)

    SciTech Connect

    Butler, J.P.; Post, G.B.; Lioy, P.J.; Waldman, J.M.; Greenberg, A. )

    1993-07-01

    The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

  18. Anti-carcinogenic potentials of a plant extract (Hydrastis canadensis): I. Evidence from in vivo studies in mice (Mus musculus).

    PubMed

    Karmakar, Susanta Roy; Biswas, Surjyo Jyoti; Khuda-Bukhsh, Anisur Rahman

    2010-01-01

    Ethanolic extract of Hydrastis canadensis has been tested for its possible anti-cancer potentials against p-dimethylaminoazobenzene (p-DAB) induced hepatocarcinogenesis in mice. Mice were chronically fed p-dimethylaminoazobenzene (p-DAB) and phenobarbital (PB), two hepato-carcinogens for 1, 2, 3 and 4 months, respectively, and were divided into sub-groups: i) fed normal low protein diet (Gr. I, normal control); ii) fed diet mixed with 0.06% p-DAB at a daily dose of 165 mg/kg b.w. per mouse plus 0.05% PB plus 0.06 ml 90% alcohol (vehicle of the crude extract) (Gr. II, carcinogen treated); iii) fed diet mixed with p-DAB and PB at the same daily dose plus crude extract of Hydrastis canadensis (Gr. III, drug treated). Several biochemical parameters like acid and alkaline phosphatases, alanine amino-, aspartate amino-, and gamma glutamyl-transferases, lipid peroxidation, reduced glutathione content, lactate dehydrogenase, catalase and glucose-6-phosphate dehydrogenase activities and electron microscopy of liver in different groups of treated and control mice were studied. A critical analysis of results of these studies suggested anti-cancer potentials of the drug suitable for use as a supportive complementary medicine in liver cancer. PMID:20843149

  19. Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer’s disease

    PubMed Central

    Hager, Klaus; Baseman, Alan S; Nye, Jeffrey S; Brashear, H Robert; Han, John; Sano, Mary; Davis, Bonnie; Richards, Henry M

    2014-01-01

    Background Currently available treatments for Alzheimer’s disease (AD) can produce mild improvements in cognitive function, behavior, and activities of daily living in patients, but their influence on long-term survival is not well established. This study was designed to assess patient survival and drug efficacy following a 2-year galantamine treatment in patients with mild to moderately severe AD. Methods In this multicenter, double-blind study, patients were randomized 1:1 to receive galantamine or placebo. One primary end point was safety; mortality was assessed. An independent Data Safety Monitoring Board monitored mortality for the total deaths reaching prespecified numbers, using a time-to-event method and a Cox-regression model. The primary efficacy end point was cognitive change from baseline to month 24, as measured by the Mini-Mental State Examination (MMSE) score, analyzed using intent-to-treat analysis with the ‘last observation carried forward’ approach, in an analysis of covariance model. Results In all, 1,024 galantamine- and 1,021 placebo-treated patients received study drug, with mean age ~73 years, and mean (standard deviation [SD]) baseline MMSE score of 19 (4.08). A total of 32% of patients (661/2,045) completed the study, 27% (554/2,045) withdrew, and 41% (830/2,045) did not complete the study and were discontinued due to a Data Safety Monitoring Board-recommended early study termination. The mortality rate was significantly lower in the galantamine group versus placebo (hazard ratio [HR] =0.58; 95% confidence interval [CI]: 0.37; 0.89) (P=0.011). Cognitive impairment, based on the mean (SD) change in MMSE scores from baseline to month 24, significantly worsened in the placebo (−2.14 [4.34]) compared with the galantamine group (−1.41 [4.05]) (P<0.001). Functional impairment, based on mean (SD) change in the Disability Assessment in Dementia score (secondary end point), at month 24 significantly worsened in the placebo (−10.81 [18

  20. AB142. Discontinuation of dapoxetine treatment in patients with premature ejaculation: a 2-year prospective observational study

    PubMed Central

    Park, Hyun Jun; Park, Nam Cheol

    2015-01-01

    Objective Although dapoxetine is the only oral pharmacological agent approved for the treatment of premature ejaculation (PE) and is very effective, its discontinuation rate is high compared to PDE5 inhibitors in patients with erectile dysfunction (ED). This study assessed the discontinuation rate of dapoxetine treatment in patients with PE and the reasons for discontinuation a clinical setting. Methods The study enrolled 182 consecutive patients [mean age, 38.2 (range, 19-63) years] between October 1, 2011 and September 30, 2013. The PE type (life-long or acquired), self-estimated intravaginal ejaculation latency time (IELT), International Index of Erectile Function-Erectile Function Domain (IIEF-EF) questionnaire, and medical history were checked in all patients. The patients were evaluated 1, 3, 6, 12, and 24 months after initiating therapy regarding the treatment status and the reasons for treatment discontinuation in the case of discontinuation. We compared the discontinuation rates with various parameters and the time interval. Results Of the patients, 9.9% were continuing treatment after 2 years. The discontinuation rate at 1, 3, 6, 12, and 24 months was 26.4%, 35.2%, 17.6%, 8.2%, and 2.7%, respectively. Cumulatively, 79.1% of the patients discontinued the treatment within 6 months. After 12 months, however, the discontinuation rate dropped sharply. The reasons for discontinuation were cost (29.9%), disappointment that PE is not a curable disease and dapoxetine was needed whenever he had sex (25%), side effects (11.6%), low efficacy (9.8%), to seek other treatment options (5.5%), and unknown (18.3%). Patients with acquired PE (vs. life-long), IELT >2 min before treatment, older than 50 years, taking PDE-5 inhibitors, and IIEF-EF <26 tended to discontinue early and had high drop-out rates. Conclusions Of the patients, 9.9% were continuing treatment after 2 years. The discontinuation rate at 1, 3, 6, 12, and 24 months was 26.4%, 35.2%, 17.6%, 8.2%, and 2

  1. Toxicity and carcinogenicity studies of Caramel Colour IV in F344 rats and B6C3F1 mice.

    PubMed

    MacKenzie, K M; Boysen, B G; Field, W E; Petsel, S R; Chappel, C I; Emerson, J L; Stanley, J

    1992-05-01

    Caramel Colour IV, a type of caramel colour used in the manufacture of cola soft drinks, was evaluated for subchronic and chronic toxicity in rats, and carcinogenicity in Fischer-344 (F344) rats and B6C3F1 mice. In each of the studies, Caramel Colour IV was mixed with demineralized water and the solutions given to the animals ad lib. in the drinking fluid. The concentrations of Caramel Colour IV in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake per kg body weight. In the range-finding studies, groups of 30 rats/sex were given Caramel Colour IV at levels of 0, 15, 20, 25 or 30 g/kg for 13 wk, and groups of 10 male rats were given levels of 0, 2.5, 5, 10 or 15 g/kg for 6 wk followed, for some dose groups, by a 2-wk withdrawal period, and then re-initiation of dosing for another 2 wk. In the rat chronic toxicity study, levels of Caramel Colour IV of 0, 2.5, 5, 7.5 or 10 g/kg were given to groups of 25 rats/sex for 12 months. The test groups in the rat and mouse carcinogenicity studies were composed of 50 animals/sex and each species was given the caramel colour at levels of 0, 0, 2.5, 5 or 10 g/kg for 24 months. In each of the studies, treated animals tended to have dose-related lower water consumption than controls. This was attributed to poor palatability of the drinking fluid, and was generally associated with decreased food consumption and body weights. Rats given caramel colour often had soft or liquid malodorous faeces although there were no treatment-related ante-mortem observations in mice. Blood biochemical changes in the rat (i.e. reduced blood urea nitrogen, alkaline phosphatase and total serum protein) appeared to be related to dietary influences and were not considered toxicologically significant. There were no treatment-related alterations in haematological variables or treatment-related differences in survival or in the incidence of benign or malignant tumours among treated and control groups and no

  2. Minimally Invasive Periodontal Treatment Using the Er,Cr: YSGG Laser. A 2-year Retrospective Preliminary Clinical Study

    PubMed Central

    Dyer, Bret; Sung, Eric C.

    2012-01-01

    Minimally invasive surgery (MIS) using the erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser (Waterlase MD, Biolase, Irvine, CA) to treat moderate to advanced periodontal disease is presented as an alternative to conventional therapies. To date, there are few short- or long-term studies to demonstrate the effects of this laser in treating and maintaining periodontal health. Electronic clinical records from 16 patients – total of 126 teeth, with pocket depths ranging from 4 mm to 9 mm – were treated with the same protocol using the Er,Cr:YSGG laser. The mean baseline probing depths (PD) were 5 mm and clinical attachment levels (CAL) were 5 mm in the 4 - 6 mm pretreated laser group. The mean baseline probing depths were 7.5 and 7.6 mm for PD and CAL respectfully in the 7 – 9 mm pretreatment laser group. At the 2 year mark, the average PD was 3.2 ± 1.1 mm for the 4-6 mm pocket group and the 7-9 mm pocket group had a mean PD of 3.7 ± 1.2 mm. mean CAL was 3.1 ± 1.1 mm for the 4-6 mm group and 3.6 ± 1.2 for the 7-9 mm group with an overall reduction of 1.9 mm and 4.0 mm respectively. At one and two years, both groups remained stable with PD comparable to the three-month gains. The CAL measurements at one and two years were also comparable to the three-month gains. PMID:22615717

  3. Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision Making of Thoracic Surgeons: A 2-year Prospective Study.

    PubMed

    Ackman, Jeanne B; Gaissert, Henning A; Lanuti, Michael; Digumarthy, Subba R; Shepard, Jo-Anne O; Halpern, Elkan F; Wright, Cameron D

    2016-08-01

    Purpose To determine the impact of nonvascular thoracic magnetic resonance (MR) imaging on the clinical decision making and diagnostic certainty of thoracic surgeons. Materials and Methods Seven thoracic surgeons at Massachusetts General Hospital, an academic quaternary referral hospital, participated in this 2-year, prospective, institution review board-approved, HIPAA-compliant pre- and post-MR imaging survey study after completing a one-time demographic survey. Between July 16, 2013, and July 13, 2015, each time a thoracic surgeon ordered a nonvascular thoracic MR imaging study via radiology order entry, he or she was sent a link to the pre-test survey that ascertained the clinical rationale for MR imaging, the clinical management plan if MR imaging was not an option, and pre-test diagnostic certainty. Upon completion of the MR imaging report, the surgeon was sent a link to the post-test survey assessing if/how MR imaging changed clinical management, the surgeon's comfort with the clinical management plan, and post-test diagnostic certainty. Data were analyzed with Student t, Wilcoxon, and McNemar tests. Results A total of 99 pre- and post-test surveys were completed. Most MR imaging studies (64 of 99 [65%]) were requested because of indeterminate computed tomographic findings. The use of MR imaging significantly reduced the number of planned surgical interventions (P < .001), modified the surgical approach in 54% (14 of 26) of surgical cases, and increased surgeon comfort with the patient management plan in 95% (94 of 99) of cases. Increased diagnostic certainty as a result of MR imaging was highly significant (P < .0001). In 21% (21 of 99) of cases, definitive MR imaging results warranted no further follow-up or clinical care. Conclusion In appropriate cases, assessment with nonvascular thoracic MR imaging substantially affects the clinical decision making and diagnostic certainty of thoracic surgeons. (©) RSNA, 2016 Online supplemental material is available

  4. Inter-species comparisons of carcinogenicity.

    PubMed Central

    Purchase, I. F.

    1980-01-01

    The carcinogenicity of 250 chemicals in 2 species, usually the rat and the mouse, was obtained from the published literature through 3 independent sources. Of the 250 compounds listed, 38% were non-carcinogenic in both rats and mice, and 44% were carcinogenic in both species. A total of 43 compounds had different results in the two species, 21 (8%) being carcinogenic in mice only, 17 (7%) in rats only and 5 (2%) having differing results from other species. A comparison of the major target organs affected by chemicals carcinogenic in both species revealed that 64% of the chemicals studied produced cancer at the same site. This comparison of carcinogenic activity in 2 species suggests that extrapolation from results in a single-animal study to man may be subject to substantial errors. PMID:7387835

  5. Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.

    PubMed

    Urano, Koji; Suzuki, Syuzo; Machida, Kazuhiko; Sawa, Nobuko; Eguchi, Natsuko; Kikuchi, Koji; Fukasawa, Kazumasa; Taguchi, Fukushi; Usui, Toshimi

    2006-12-01

    We studied the effect of IC tags, subcutaneously implanted animal identification tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and 75 female non-Tg mice from the same litter as the rasH2 mice divided into a non-IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of the animals except for those in the non-IC tag group) had IC tags implanted subcutaneously in their backs. The administration methods of the positive control drugs TPA (2.5 micro g/kg, 3 times/week, percutaneously) and MNU (75 mg/kg, single intraperitoneal injection) were based on the protocol of the ILSI/HESI international collaborative study. The results showed no differences in the tumorigenic incidence and organs developing tumors between the IC tag and non-IC tag groups in both rasH2 and non-Tg mice. In the positive control MNU group, the tumorigenic incidence and organs developing tumors were the same as the background data and no promotion of carcinogenesis was observed. In all IC tag groups including the TPA group and MNU group, a fibrous capsule was formed around the IC tags subcutaneously, but no inflammatory changes or neoplastic changes were observed. From these findings, it was concluded that the IC tag has no effect on a 26-week carcinogenicity test of rasH2 mice under the conditions of the present study. PMID:17202757

  6. Listing Occupational Carcinogens

    PubMed Central

    Siemiatycki, Jack; Richardson, Lesley; Straif, Kurt; Latreille, Benoit; Lakhani, Ramzan; Campbell, Sally; Rousseau, Marie-Claude; Boffetta, Paolo

    2004-01-01

    The occupational environment has been a most fruitful one for investigating the etiology of human cancer. Many recognized human carcinogens are occupational carcinogens. There is a large volume of epidemiologic and experimental data concerning cancer risks in different work environments. It is important to synthesize this information for both scientific and public health purposes. Various organizations and individuals have published lists of occupational carcinogens. However, such lists have been limited by unclear criteria for which recognized carcinogens should be considered occupational carcinogens, and by inconsistent and incomplete information on the occupations and industries in which the carcinogenic substances may be found and on their target sites of cancer. Based largely on the evaluations published by the International Agency for Research on Cancer, and augmented with additional information, the present article represents an attempt to summarize, in tabular form, current knowledge on occupational carcinogens, the occupations and industries in which they are found, and their target organs. We have considered 28 agents as definite occupational carcinogens, 27 agents as probable occupational carcinogens, and 113 agents as possible occupational carcinogens. These tables should be useful for regulatory or preventive purposes and for scientific purposes in research priority setting and in understanding carcinogenesis. PMID:15531427

  7. Retrospective cohort study between selective and standard C3-7 laminoplasty. Minimum 2-year follow-up study

    PubMed Central

    Asazuma, Takashi; Masuoka, Kazunori; Yasuoka, Hiroki; Motosuneya, Takao; Sakai, Tsubasa; Nemoto, Koichi

    2007-01-01

    A total of 64 patients with cervical spondylotic myelopathy (CSM) were assessed in this study. Forty-two patients underwent selective expansive open-door laminoplasty (ELAP). Twenty-two patients who underwent conventional C3-7 ELAP served as controls. There were no significant differences in recovery rate of JOA scores, C2–C7 angle or cervical range of motion between two groups. Incidence of axial symptoms and segmental motor paralysis in selective ELAP was significantly lower than those in the C3-7 ELAP. Size of anterior compression mass, postoperative spinal cord positions and decompression conditions were evaluated using preoperative or postoperative MRI in 50 of 64 patients. There was a positive correlation between number of expanded laminae and maximum anterior spaces of spinal cord. Incomplete decompression was developed in three of 37 patients in selective ELAP and in two of 13 patients in C3-7ELAP. Mean size of anterior compression mass at incomplete decompression levels was significantly greater than that at complete decompression levels. Since, there was less posterior movement of the spinal cord in selective ELAP than that in C3-7ELAP, minute concerns about size of anterior compression mass is necessary to decide the number of expanded laminae. Overall, selective ELAP was less invasive and useful in reducing axial symptoms and segmental motor paralysis. This new surgical strategy was effective in improving the surgical outcomes of CSM, and short-term results were satisfactory. PMID:17726618

  8. The carcinogenicity of arsenic.

    PubMed Central

    Pershagen, G

    1981-01-01

    A carcinogenic role of inorganic arsenic has been suspected for nearly a century. Exposure to inorganic arsenic compounds occurs in some occupational groups, e.g., among smelter workers and workers engaged in the production and use of arsenic containing pesticides. Substantial exposure can also result from drinking water in certain areas and the use of some drugs. Tobacco and wine have had high As concentrations due to the use of arsenic containing pesticides. Inorganic arsenic compounds interfere with DNA repair mechanisms and an increased frequency of chromosomal aberrations have been observed among exposed workers and patients. Epidemiological data show that inorganic arsenic exposure can cause cancer of the lung and skin. The evidence of an etiologic role of arsenic for angiosarcoma of the liver is highly suggestive; however, the association between arsenic and cancer of other sites needs further investigation. No epidemiological data are available on exposure to organic arsenic compounds and cancer. Animal carcinogenicity studies involving exposure to various inorganic and organic arsenic compounds by different routes have been negative, with the possible exception of some preliminary data regarding lung cancer and leukemia. Some studies have indicated an increased mortality from lung cancer in populations living near point emission sources of arsenic into the air. The role of arsenic cannot be evaluated due to lack of exposure data. Epidemiological data suggest that the present WHO standard for drinking water (50 micrograms As/l.) provides only a small safety margin with regard to skin cancer. PMID:7023936

  9. Transcriptome Analysis in Peripheral Blood of Humans Exposed to Environmental Carcinogens: A Promising New Biomarker in Environmental Health Studies

    PubMed Central

    van Leeuwen, Danitsja M.; Gottschalk, Ralph W.H.; Schoeters, Greet; van Larebeke, Nicolas A.; Nelen, Vera; Baeyens, Willy F.; Kleinjans, Jos C.S.; van Delft, Joost H.M.

    2008-01-01

    Background Human carcinogenesis is known to be initiated and/or promoted by exposure to chemicals that occur in the environment. Molecular cancer epidemiology is used to identify human environmental cancer risks by applying a range of effect biomarkers, which tend to be nonspecific and do not generate insights into underlying modes of action. Toxicogenomic technologies may improve on this by providing the opportunity to identify molecular biomarkers consisting of altered gene expression profiles. Objectives The aim of the present study was to monitor the expression of selected genes in a random sample of adults in Flanders selected from specific regions with (presumably) different environmental burdens. Furthermore, associations of gene expression with blood and urinary measures of biomarkers of exposure, early phenotypic effects, and tumor markers were investigated. Results Individual gene expression of cytochrome p450 1B1, activating transcription factor 4, mitogen-activated protein kinase 14, superoxide dismutase 2 (Mn), chemokine (C-X-C motif) lig-and 1 (melanoma growth stimulating activity, alpha), diacylglycerol O-acyltransferase homolog 2 (mouse), tigger transposable element derived 3, and PTEN-induced putative kinase1 were measured by means of quantitative polymerase chain reaction in peripheral blood cells of 398 individuals. After correction for the confounding effect of tobacco smoking, inhabitants of the Olen region showed the highest differences in gene expression levels compared with inhabitants from the Gent and fruit cultivation regions. Importantly, we observed multiple significant correlations of particular gene expressions with blood and urinary measures of various environmental carcinogens. Conclusions Considering the observed significant differences between gene expression levels in inhabitants of various regions in Flanders and the associations of gene expression with blood or urinary measures of environmental carcinogens, we conclude that

  10. Carcinogenicity of hair dye components.

    PubMed

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer. PMID:6993608

  11. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... a cause for concern if not seen by 2 years.) Can run with better coordination . (May still ...

  12. Developmental milestones record - 2 years

    MedlinePlus

    Growth milestones for children - 2 years; Normal childhood growth milestones - 2 years; Childhood growth milestones - 2 years ... cause for concern if not seen by 2 years.) Can run with better coordination. (May still have ...

  13. Validation of transgenic mice carrying the human prototype c-Ha-ras gene as a bioassay model for rapid carcinogenicity testing.

    PubMed Central

    Yamamoto, S; Urano, K; Koizumi, H; Wakana, S; Hioki, K; Mitsumori, K; Kurokawa, Y; Hayashi, Y; Nomura, T

    1998-01-01

    Carcinogenicity testing is indispensable for identifying environmental carcinogens and for evaluating the safety of drugs in the process of development. Conventional 2-year rodent bioassays are one of the most resource-consuming tests in terms of animals, time, and costs. Development of rapid carcinogenicity testing systems that can assess carcinogenicity within a short period has become a social demand and is essential to improve efficacy in the identification of environmental carcinogens as well as in the development of new drugs. In this review we introduce the rapid carcinogenicity testing system using transgenic (Tg) mice carrying the human prototype c-Ha-ras gene, namely rasH2 mouse (CB6F1-TgHras2 mouse is the same mouse). The studies have been conducted to validate the rasH2 mouse as a model for the rapid carcinogenicity testing system. Our current validation studies revealed that rasH2 mice are able to detect various types of mutagenic carcinogens within 6 months. The rasH2 mice may also be able to detect various nonmutagenic carcinogens. The validation studies also revealed that rasH2 mice are generally much more susceptible to both mutagenic and nonmutagenic carcinogens than control non-Tg mice. No significant tumor induction has been observed in rasH2 mice with either mutagenic or nonmutagenic noncarcinogens. More rapid onset and higher incidence of more malignant tumors can be expected with a high probability after treatment with various carcinogens in the rasH2 mice than in control non-Tg mice. The rasH2 mouse appears to be a promising candidate as an animal model for development of a rapid carcinogenicity testing system. PMID:9539005

  14. Evaluation of the Xpa-deficient transgenic mouse model for short-term carcinogenicity testing: 9-month studies with haloperidol, reserpine, phenacetin, and D-mannitol.

    PubMed

    Lina, Ben A R; Woutersen, Ruud A; Bruijntjes, Joost P; van Benthem, Jan; van den Berg, Jolanda A H; Monbaliu, Johan; Thoolen, Bob J J M; Beems, Rudolf B; van Kreijl, Coen F

    2004-01-01

    As part of the international evaluation program coordinated by ILSI/HESI, the potential of DNA repair deficient Xpa-/- mice and the double knockout Xpa-/-.p53+/- mice for short term carcinogenicity assays was evaluated. For comparison also wild-type C57BL/6 mice (WT) were included in these studies. Four test compounds were administered to groups of 15 male and 15 female Xpa-/- mice, Xpa-/-.p53+/- mice and WT mice for 39 weeks. The model compounds investigated were haloperidol, reserpine (nongenotoxic rodent carcinogens, putative human noncarcinogens), phenacetin (genotoxic rodent carcinogen, suspected human carcinogen), and D-mannitol (noncarcinogen in rodents and humans). The test compounds were administered as admixture to rodent diet at levels up to 25 mg/kg diet for haloperidol, 7.5 mg/kg diet for reserpine, 0.75% for phenacetin, and 10% for D-mannitol. These levels included the maximum tolerable dose (MTD). Survival was not affected with any of the test compounds. Haloperidol, reserpine and D-mannitol were negative in the carcinogenicity assay with Xpa-/- and Xpa-/-.p53+/- mice, showing low and comparable tumor incidences in controls and high-dose animals. The results obtained with phenacetin may be designated equivocal in Xpa-/-.p53+/- mice, based on the occurrence of a single rare tumor in the target organ (kidney) accompanied by a low incidence of hyperplastic renal lesions and a high incidence of karyomegaly. These results are in agreement with the currently known carcinogenic potential of the 4 test compounds in humans. PMID:15200157

  15. Long-Term Outcomes of a Web-Based Diabetes Prevention Program: 2-Year Results of a Single-Arm Longitudinal Study

    PubMed Central

    Jiang, Luohua; Peters, Anne L

    2015-01-01

    Background Digital therapeutics are evidence-based behavioral treatments delivered online that can increase accessibility and effectiveness of health care. However, few studies have examined long-term clinical outcomes of digital therapeutics. Objective The objective of this study was to conduct a 2-year follow-up on participants in the Internet-based Prevent diabetes prevention program pilot study, specifically examining the effects on body weight and A1c, which are risk factors for diabetes development. Methods A quasi-experimental research design was used, including a single-arm pre- and post-intervention assessment of outcomes. Participants underwent a 16-week weight loss intervention and an ongoing weight maintenance intervention. As part of the program, participants received a wireless scale, which was used to collect body weight data on an ongoing basis. Participants also received A1c test kits at baseline, 0.5 year, 1 year, and 2-year time points. Results Participants previously diagnosed with prediabetes (n=220) were originally enrolled in the pilot study. A subset of participants (n=187) met Centers for Disease Control and Prevention (CDC) criteria for starting the program (starters), and a further subset (n=155) met CDC criteria for completing the program (completers) and were both included in analyses. Program starters lost an average of 4.7% (SD 0.4) of baseline body weight after 1 year and 4.2% (SD 0.8) after 2 years, and reduced A1c by mean 0.38% (SD 0.07) after 1 year and 0.43% (SD 0.08) after 2 years. Program completers lost mean 4.9% (SD 0.5) of baseline body weight after 1 year and 4.3% (SD 0.8) after 2 years, and reduced A1c by 0.40% (SD 0.07) after 1 year and 0.46% (SD 0.08) after 2 years. For both groups, neither 2-year weight loss nor A1c results were significantly different from 1-year results. Conclusions Users of the Prevent program experienced significant reductions in body weight and A1c that are maintained after 2 years. Contrary to the

  16. Iron-Folic Acid Supplementation During Pregnancy Reduces the Risk of Stunting in Children Less Than 2 Years of Age: A Retrospective Cohort Study from Nepal

    PubMed Central

    Nisar, Yasir Bin; Dibley, Michael J.; Aguayo, Victor M.

    2016-01-01

    The aim of the study was to investigate the effect of antenatal iron-folic acid (IFA) supplementation on child stunting in Nepalese children age <2 years. A retrospective cohort study design was used, in which a pooled cohort of 5235 most recent live births 2 years prior to interview from three Nepal Demographic and Health Surveys (2001, 2006 and 2011) was analysed. The primary outcome was stunting in children age <2 years. The main exposure variable was antenatal IFA supplementation. Multivariate Poisson regression analysis was performed. In our sample, 31% and 10% of Nepalese children age <2 years were stunted and severely stunted, respectively. The adjusted relative risk of being stunted was 14% lower in children whose mothers used IFA supplements compared to those whose mothers did not use (aRR = 0.86, 95% CI = 0.77–0.97). Additionally, the adjusted relative risk of being stunted was significantly reduced by 23% when antenatal IFA supplementation was started ≤6 months with ≥90 IFA supplements used during pregnancy (aRR = 0.77, 95% CI = 0.64–0.92). Antenatal IFA supplementation significantly reduced the risk of stunting in Nepalese children age <2 years. The greatest impact on the risk reduction of child stunting was when IFA supplements were started ≤6 months with ≥90 supplements were used. PMID:26828515

  17. Continuity, Comorbidity and Longitudinal Associations between Depression and Antisocial Behaviour in Middle Adolescence: A 2-Year Prospective Follow-Up Study

    ERIC Educational Resources Information Center

    Ritakallio, Minna; Koivisto, Anna-Maija; von der Pahlen, Bettina; Pelkonen, Mirjami; Marttunen, Mauri; Kaltiala-Heino, Riittakerttu

    2008-01-01

    The study investigated continuity, comorbidity and longitudinal associations between depression Beck depression inventory (RBDI) and antisocial behaviour Youth self-report (YSR) in middle adolescence. Data were used from a community sample of 2070 adolescents who participated in a 2-year prospective follow-up study. The results indicate that both…

  18. TOPICAL REVIEW: MUTAGENICITY AND CARCINOGENICITY OF AIR

    EPA Science Inventory

    Although both outdoor and indoor airs provide exposure to mutagens and carcinogens, this review shows that the level of hazard is highly variable. Outdoor air was first shown to be carcinogenic in 1942 and mutagenic in 1975; and studies examining the genotoxicity of indoor air so...

  19. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    SciTech Connect

    Jackson, Anna Francina; Williams, Andrew; Recio, Leslie; Waters, Michael D.; Lambert, Iain B.; Yauk, Carole L.

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun in response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF

  20. Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.

    PubMed

    Ruano-Ravina, Alberto; García-Lavandeira, José Antonio; Torres-Durán, María; Prini-Guadalupe, Luciana; Parente-Lamelas, Isaura; Leiro-Fernández, Virginia; Montero-Martínez, Carmen; González-Barcala, Francisco Javier; Golpe-Gómez, Antonio; Martínez, Cristina; Castro-Añón, Olalla; Mejuto-Martí, María José; Barros-Dios, Juan Miguel

    2014-07-01

    We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer. PMID:24742725

  1. SPONTANEOUS OCCURRENCE OF A DISTINCTIVE RENAL TUBULE TUMOR PHENOTYPE IN RAT CARCINOGENICITY STUDIES CONDUCTED BY THE NATIONAL TOXICOLOGY PROGRAM (NTP)

    PubMed Central

    Hard, Gordon C; Seely, John Curtis; Kissling, Grace E; Betz, Laura J

    2010-01-01

    The Toxicology Data Management System (TDMS) of the National Toxicology Program, NIEHS, NIH, was surveyed for occurrence and distribution of a distinctive renal tubule tumor type in rats. The hallmark features of this tumor included eosinophilic/amphophilic staining, large finely granular cells, and numerous vacuoles and/or minilumens. It is referred to here as the amphophilic-vacuolar (AV) variant of renal tubule tumor. Of 154 studies in which renal tubule tumors had been recorded in the standard single sections of kidney in the TDMS, there were collectively 1012 rats with renal adenomas, carcinomas or adenocarcinomas, and of these, 100 displayed the distinctive AV morphology, representing 74 studies involving mostly the F344 rat, but also the Sprague-Dawley and Wistar strains. The AV tumors (mainly adenomas but also some carcinomas) occurred usually as solitary lesions in the affected animals. However, they were multiple and bilateral in a few cases. They were equally distributed between the sexes, did not metastasize (at least to the lung), and were not associated with chronic progressive nephropathy. The distribution of this renal tumor type was random across studies and dose groups, underscoring the likelihood that it was of spontaneous origin and not chemically induced. Accordingly, it is suggested that this distinctive renal tumor phenotype be recorded as a separate category from conventional RTT when assessing the carcinogenic potential of a test compound. PMID:18441261

  2. Do Deviant Peer Associations Mediate the Contributions of Self-Esteem to Problem Behavior During Early Adolescence? A 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    DuBois, David L.; Silverthorn, Naida

    2004-01-01

    We investigated deviant peer associations as a mediator of the influences of general and peer-oriented self-esteem on problem behavior using data from a 2-year longitudinal study of 350 young adolescents. Measures of problem behavior included substance use (alcohol use, smoking) and antisocial behavior (fighting, stealing). Using latent growth…

  3. The Role of Pictures and Gestures as a Support Mechanism for Novel Word Learning: A Training Study with 2-Year-Old Children

    ERIC Educational Resources Information Center

    Kapalková, Svetlana; Polišenská, Kamila; Süssová, Martina

    2016-01-01

    A training study examined novel word learning in 2-year-old children and assessed two nonverbal mechanisms, pictures and gestures, which are commonly used as communication support. The aim was to (1) compare these two support mechanisms and measure their effects on expressive word learning and (2) to investigate these effects on word production…

  4. Exploring the Relationship between Autistic-Like Traits and ADHD Behaviors in Early Childhood: Findings from a Community Twin Study of 2-Year-Olds

    ERIC Educational Resources Information Center

    Ronald, Angelica; Edelson, Lisa R.; Asherson, Philip; Saudino, Kimberly J.

    2010-01-01

    Behaviors characteristic of autism and ADHD emerge in early childhood, yet research investigating their comorbidity has focused on older children. This study aimed to explore the nature of the relationship between autistic-like traits and ADHD behaviors in a community sample of 2-year-olds. Twins from the Boston University Twin Project (N = 312…

  5. Toxico-Cheminformatics and QSPR Modeling of the Carcinogenic Potency Database

    EPA Science Inventory

    Report on the development of a tiered, confirmatory scheme for prediction of chemical carcinogenicity based on QSAR studies of compounds with available mutagenic and carcinogenic data. For 693 such compounds from the Carcinogenic Potency Database characterized molecular topologic...

  6. PREDICTING RODENT CARCINOGENICITY OF HALOGENATED HYDROCARBON BY IN VIVO BIOCHEMICAL PARAMETERS

    EPA Science Inventory

    Forty halogenated hydrocarbons of known rodent carcinogenicity (24 carcinogens, 16 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens and hepatocarcinogens were selected for study. he effects of these 40 chemicals on four biochemical assays (hep...

  7. A retrospective study of radiographic abnormalities in the repositories of 2-year-old Thoroughbred in-training sales in Japan

    PubMed Central

    MIYAKOSHI, Daisuke; SENBA, Hiroyuki; SHIKICHI, Mitsumori; MAEDA, Masaya; SHIBATA, Ryo; MISUMI, Kazuhiro

    2016-01-01

    ABSTRACT This study aimed to evaluate the influence of radiographic abnormalities of 2-year-old Thoroughbred horses that were listed at in-training sales in Japan, on whether they started to race or not at 2–3 years of age. Radiographs of 850 2-year-old Thoroughbreds in the in-training sales repository from 2007 to 2010 were reviewed, and 26 categories of radiographic abnormalities were found. Forty-three horses (5.1%, 43/850) did not start a race at 2–3 years of age. In accordance with the racing results for this age category, as determined by Fisher’s exact test and multiple logistic regression analysis, none of the radiographic abnormalities were significantly related to failure to start a race. At 2 years of age, 198 horses (23.3%, 198/850) did not start a race. Horses with enlargement of the proximal sesamoid bones in the fore (9 of 19 horses) and hind limbs (5 of 9 horses) did not start a race at the age of 2 years, and fewer of these horses (fore, P=0.021; hind, P=0.030) started a race at the age of 2 years compared with the population of horses without these radiographic abnormalities. These results suggest that identification of radiographic enlargement of the proximal sesamoid bones during training sales could derail the racing debut of horses at the age of 2 years. However, this might not necessarily indicate a poor prognosis and resulting in retirement from racing at 2–3 years of age. PMID:27330400

  8. Risk assessment of carcinogens in food

    SciTech Connect

    Barlow, Susan

    2010-03-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a 'margin of exposure' approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  9. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF ARSENIC COMPOUNDS

    EPA Science Inventory

    Arsenic and inorganic compounds a human carcinogens, classified as weight-of-evidence Group A under the EPA Guidelines for Carcinogen Risk Assessment. vidence on potential carcinogenicity from animal studies is "Inadequate," and the evidence from human studies is "Sufficient." rs...

  10. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF N-NITROSODIETHANO-LAMINE

    EPA Science Inventory

    N-Nitrosodiethanolamine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient," and the evidence from human studi...

  11. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF COKE OVEN EMISSIONS

    EPA Science Inventory

    Coke oven emissions are known human carcinogens, classified as weight-of-evidence Group A under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient,". and the evidence rom human studies is "S...

  12. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF 1,2-DIETHYLHYDRAZINE

    EPA Science Inventory

    1,2-Diethylhydrazine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient", and the evidence from human studies ...

  13. How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study.

    PubMed

    Anthony Tony Cox, Louis; Popken, Douglas A; Kaplan, A Michael; Plunkett, Laura M; Becker, Richard A

    2016-06-01

    A recent research article by the National Center for Computational Toxicology (NCCT) (Kleinstreuer et al., 2013), indicated that high throughput screening (HTS) data from assays linked to hallmarks and presumed pathways of carcinogenesis could be used to predict classification of pesticides as either (a) possible, probable or likely rodent carcinogens; or (b) not likely carcinogens or evidence of non-carcinogenicity. Using independently developed software to validate the computational results, we replicated the majority of the results reported. We also found that the prediction model correlating cancer pathway bioactivity scores with in vivo carcinogenic effects in rodents was not robust. A change of classification of a single chemical in the test set was capable of changing the overall study conclusion about the statistical significance of the correlation. Furthermore, in the subset of pesticide compounds used in model validation, the accuracy of prediction was no better than chance for about three quarters of the chemicals (those with fewer than 7 positive outcomes in HTS assays representing the 11 histopathological endpoints used in model development), suggesting that the prediction model was not adequate to predict cancer hazard for most of these chemicals. Although the utility of the model for humans is also unclear because a number of the rodent responses modeled (e.g., mouse liver tumors, rat thyroid tumors, rat testicular tumors, etc.) are not considered biologically relevant to human responses, the data examined imply the need for further research with HTS assays and improved models, which might help to predict classifications of in vivo carcinogenic responses in rodents for the pesticide considered, and thus reduce the need for testing in laboratory animals. PMID:26879462

  14. Comparison of in vivo genotoxic and carcinogenic potency to augment mode of action analysis: Case study with hexavalent chromium.

    PubMed

    Thompson, Chad M; Bichteler, Anne; Rager, Julia E; Suh, Mina; Proctor, Deborah M; Haws, Laurie C; Harris, Mark A

    2016-04-01

    Recent analyses-highlighted by the International Workshops on Genotoxicity Testing Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment-have identified a correlation between (log) estimates of a carcinogen's in vivo genotoxic potency and in vivo carcinogenic potency in typical laboratory animal models, even when the underlying data have not been matched for tissue, species, or strain. Such a correlation could have important implications for risk assessment, including informing the mode of action (MOA) of specific carcinogens. When in vivo genotoxic potency is weak relative to carcinogenic potency, MOAs other than genotoxicity (e.g., endocrine disruption or regenerative hyperplasia) may be operational. Herein, we review recent in vivo genotoxicity and carcinogenicity data for hexavalent chromium (Cr(VI)), following oral ingestion, in relevant tissues and species in the context of the aforementioned correlation. Potency estimates were generated using benchmark doses, or no-observable-adverse-effect-levels when data were not amenable to dose-response modeling. While the ratio between log values for carcinogenic and genotoxic potency was ≥1 for many compounds, the ratios for several Cr(VI) datasets (including in target tissue) were less than unity. In fact, the ratios for Cr(VI) clustered closely with ratios for chloroform and diethanolamine, two chemicals posited to have non-genotoxic MOAs. These findings suggest that genotoxicity may not play a major role in the cancers observed in rodents following exposure to high concentrations of Cr(VI) in drinking water-a finding consistent with recent MOA and adverse outcome pathway (AOP) analyses concerning Cr(VI). This semi-quantitative analysis, therefore, may be useful to augment traditional MOA and AOP analyses. More case examples will be needed to further explore the general applicability and validity of this approach for human health risk assessment. PMID:27085472

  15. Predictive testing of environmental carcinogens

    SciTech Connect

    Dickson, J.G.

    1982-01-01

    Two research approaches are presented which address different aspects of predictive testing for environmental carcinogens. In Part I, a well-known microbial assay is used to determine the presence of carcinogens in an environmental sample of suspected hazard. In Part II, a single chemical carcinogen is chosen to demonstrate the utility of three-phase microcosms for prediction of transport and transformations pathways in a reservoir ecosystem. The Ames/Salmonella mutagenicity assay was used to screen processed oil shale extracts for potentially carcinogenic chemicals. Positive mutagenic activity was detected in organic solvent extracts of all four spent shales tested. Problems which might limit application of the Ames assay were explored. The results of assays of one-to-one mixtures of two mutagens which exhibited different dose response curves when assayed separately indicated the response to the mixture was nonadditive. Furthermore, the response to the mixture was determined to be statistically indistinguishable (chi-square analysis) from the dose response curve of one of the mutagens in the majority of cases. This masking effect was found to persist for one strong mutagen (benzo(a)pyrene) even when it composed only 10% of the mixture. The effect of various non-toxic solvents on the mutagenic response of certain mutagens was also determined. Three-phase microcosms were used to study the aquatic fate and effect of a polycyclic aromatic hydrocarbon (PAH), benz(a)antracene.

  16. Genotoxicity studies with the unstable Zeste-White (UZ) system of Drosophila melanogaster: Results with ten carcinogenic compounds

    SciTech Connect

    Batiste-Alentorn, M.; Xamena, N.; Creus, A.; Marcos, R. )

    1991-01-01

    To increase the number of chemicals tested using the Zeste-White (UZ) somatic mutation assay, ten selected carcinogens (acetamide, acrylamide, benzo({alpha})pyrene, cyclophosphamide, diethylstilbestrol, 4-nitroquinoline N-oxide, propyleneimine, safrole, thiourea, and o-toluidine) have been evaluated in this assay. The results show that all the compounds tested produce significant increases in the eye spot frequency at, at least, one of the concentrations assayed, indicating that the Zeste-White assay appears to be highly sensitive to these carcinogenic compounds. That is in agreement with data previously reported by other authors.

  17. Trait and State Attributes of Insight in First Episodes of Early-Onset Schizophrenia and Other Psychoses: A 2-Year Longitudinal Study

    PubMed Central

    Parellada, Mara; Boada, Leticia; Fraguas, David; Reig, Santiago; Castro-Fornieles, Josefina; Moreno, Dolores; Gonzalez-Pinto, Ana; Otero, Soraya; Rapado-Castro, Marta; Graell, Montserrat; Baeza, Inmaculada; Arango, Celso

    2011-01-01

    Background: Increasing evidence supports the important role of illness state and individual characteristics in insight. Methods: Insight, as measured with the Scale to Assess Unawareness of Mental Disorder, over the first 2 years of early-onset first-episode psychosis and its correlations with clinical, socio-demographic, cognitive, and structural brain variables are studied. Results: (1) insight at 2 years is poorer in schizophrenia spectrum disorders (SSDs) than in subjects with other psychoses; (2) the more severe the psychosis, the worse the insight. In SSD, depressive symptoms, poorer baseline executive functioning, lower IQ, longer duration of untreated psychosis (DUP), and poorer premorbid infancy adjustment are associated with poorer insight; frontal and parietal gray matter (GM) reductions at baseline correlate with worse insight into having psychotic symptoms at 2 years; (3) insight into having a mental disorder (Scale to Assess Unawareness of Mental Disorder [SUMD]1) at 1 year, DUP, and baseline IQ are the most consistent variables explaining different aspects of insight at 2 years in SSD patients. IQ and SUMD1 at 1 year, together with left frontal and parietal GM volumes, explain 80% of the variance of insight into having specific psychotic symptoms in SSD patients (adjusted R2 = 0.795, F = 15.576, P < .001). Conclusion: Insight is a complex phenomenon that depends both on severity of psychopathology and also on disease and subject characteristics, such as past adjustment, IQ, DUP, cognitive functioning, frontal and parietal GM volumes, and age, gender, and ethnicity. PMID:20884756

  18. Diurnal Cortisol Secretion at Home and in Child Care: A Prospective Study of 2-Year-Old Toddlers

    ERIC Educational Resources Information Center

    Ouellet-Morin, Isabelle; Tremblay, Richard E.; Boivin, Michel; Meaney, Michael; Kramer, Michael; Cote, Sylvana M.

    2010-01-01

    Background: Previous studies indicate that children may experience disrupted cortisol secretion in child care. The extent to which this is a transient or long-term disruption is not known, as most studies have relied on cross-sectional designs, and age-heterogeneous small sample sizes. This study aims to (a) compare cortisol secretion measured at…

  19. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  20. Comparative biochemical and electron-microscopic study of membrane damage to the endoplasmic reticulum by a chemical carcinogen in vivo and in vitro

    SciTech Connect

    Merkur'eva, R.V.; Dolinskaya, S.I.; Shekhtman, A.B.; Gasanov, T.G.; Gadzhieva, T.I.; Shakmirova, S.F.

    1987-07-01

    Results are given of a comparative biochemical and electron-microscopic study of the membrane-damaging action of the chemical carcinogen N-nitrosodimethylamine (NDMA), as a result of exposure in vivo and in vitro. Experiments were carried out on rats. A characteristic feature of development of the biological effect of NDMA both in vivo and in vitro is a decrease in activity of the membrane-bound enzymes of the endoplasmic reticulum chosen for study.

  1. The Role of Behavioral Self-Regulation in Learning to Read: A 2-Year Longitudinal Study of Icelandic Preschool Children

    ERIC Educational Resources Information Center

    Birgisdóttir, Freyja; Gestsdóttir, Steinunn; Thorsdóttir, Fanney

    2015-01-01

    Research Findings: Research suggests that behavioral self-regulation skills are critical for early school success, including success in literacy, but few studies have explored the relations that behavioral self-regulation may have with different components of early literacy development. The present study investigated the longitudinal contribution…

  2. Line narrowing spectroscopic studies of DNA-carcinogen adducts and DNA-dye complexes

    SciTech Connect

    Suh, Myungkoo

    1995-12-06

    Laser-induced fluorescence line narrowing and non-line narrowing spectroscopic methods were applied to conformational studies of stable DNA adducts of the 7{beta}, 8{alpha}-dihydoxy-9{alpha}, l0{alpha}-epoxy-7,8,9, 10-tetrahydrobenzo[{alpha}]pyrene (anti-BPDE). Stereochemically distinct (+)-trans-, ({minus})-trans-, (+)-cis- and ({minus})-cis adducts of anti-BPDE bound to exocyclic amino group of the central guanine in an 11-mer oligonucleotide, exist in a mixture of conformations in frozen aqueous buffer matrices. The (+)-trans adduct adopts primarily an external conformation with a smaller fraction ( {approximately} 25 %) exists in a partially base-stacked conformation. Both cis adducts were found to be intercalated with significant {pi}-{pi} stacking interactions between the pyrenyl residues and the bases. Conformations of the trans-adduct of (+)-anti -BPDE in 11-mer oligonucleotides were studied as a function of flanking bases. In single stranded form the adduct at G{sub 2} or G{sub 3} (5 ft-flanking, base guanine) adopts a conformation with strong, interaction with the bases. In contrast, the adduct with a 5ft-flanking, thymine exists in a primarily helixexternal conformation. Similar differences were observed in the double stranded oligonucleotides. The nature of the 3ft-flanking base has little influence on the conformational equilibrium of the (+)-trans-anti BPDE-dG adduct. The formation and repair of BPDE-N{sup 2}-dG in DNA isolated from the skin of mice treated topically with benzo[{alpha}]pyrene (BP) was studied. Low-temperature fluorescence spectroscopy of the intact DNA identified the major adduct as (+)-trans-anti-BPDE-N-dG, and the minor adduct fraction consisted mainly of (+)-cis-anti-BPDE-N{sup 2}-dG.

  3. An Evaluation of the Mode of Action Framework for MutagenicCarcinogens Case Study II: Chromium (VI).

    EPA Science Inventory

    In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to include all mutagenicity and other genotoxicity data with any additional information to determine whether a carcinogen operates through a mutagenic mode...

  4. Results of current intraperitoneal carcinogenicity studies with mineral and vitreous fibres.

    PubMed

    Roller, M; Pott, F; Kamino, K; Althoff, G H; Bellmann, B

    1996-01-01

    The study includes some 50 groups of male or female Wistar rats tested in three series. Except for one untreated group and 3 vehicle control groups, the animals were injected intraperitoneally (i.p.) once or repeatedly with dust suspensions and then examined, after lifetime observation up to 30 months, for tumours in the abdominal cavity. 1 granular dust (silicon carbide), 2 asbestos dusts (crocidolite, tremolite) and 11 vitreous fibre dust samples were administered. 5 of the vitreous fibre types were fine fibre fractions from 4 commercial insulation wools and 1 experimental wool, the others were prepared by milling glass microfibres, which have, per se, a small diameter range. The dosage per rat differed over a wide range in accordance with experience from earlier studies. The lowest dose was 0.04 x 10(9) crocidolite fibres in 0.5 mg dust, and the highest amounted to 20 x 10(9) glass fibres in 1000 mg divided into 40 weekly injections. Two mesotheliomas were found in a total of 395 rats treated with saline or granular silicon carbide (250 or 1000 mg). Eleven fibre dusts produced dose-dependent mesotheliomas at rates of up to 97 %, but the calculated fibre number > 5 micrometers in length required for inducing a 25 % tumour risk differed between the fibre samples tested in the relation of 1 to about 1000. UICC-like crocidolite heads the ranking order; the glass fibre B-01, which possesses a low durability in the body, ends it together with a rather thin sample of glass fibre type B-09. The stone fibre MMVF-21 takes a high place in the ranking order, similar to the tremolite sample. The results correspond to those of earlier i.p. tests. PMID:8919265

  5. In silico study of anti-carcinogenic lysyl oxidase-like 2 inhibitors.

    PubMed

    Muhammad, Syed Aun; Ali, Amjad; Ismail, Tariq; Zafar, Rehan; Ilyas, Umair; Ahmad, Jamil

    2014-08-01

    Lysyl oxidase homolog 2 (LOXL2), also known as lysyl oxidase-like protein 2 is recently been explored as regulator of carcinogenesis and has been shown to be involved in tumor progression and metastasis of several carcinomas. Therefore LOXL2 has been considered as potential therapeutic target. Doing so, its inhibitors as new chemotherapeutic lead molecules: 4-amino-5-(2-hydroxyphenyl)-1,2,4-triazol-3-thione (2a) and 4-(2-hydroxybenzalidine) amine-5-(2-hydroxy) phenyl-1,2,4-triazole-3-thiol (2b) are synthesized by fusion method (refluxed at 160 °C). Spectral analysis of these triazole derivatives are characterized by FTIR and NMR. Active binding sites and quality of the LOXL2 model is assessed by Ramachandran plots and finally drug-target analysis is performed by computational virtual screening tools. Compounds 2a and 2b showed optimum target binding affinity with -6.2 kcal/mol and -8.9 kcal/mol binding energies. This insilico study will add to our understanding of the drug designing and development, and to target cancer-causing proteins more precisely and quickly than before. PMID:24703812

  6. Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

    PubMed

    Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

    2013-07-01

    Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. PMID:22161475

  7. Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

    PubMed Central

    Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

    2011-01-01

    Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m3 for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints. PMID:21432714

  8. The Predictive Relationship between Temperament, School Adjustment, and Academic Achievement: A 2-Year Longitudinal Study of Children At-Risk

    ERIC Educational Resources Information Center

    Al-Hendawi, Maha

    2010-01-01

    Individual differences in temperament can be a risk or a protective factor for a child, especially for children at-risk who possess single or multiple risk factors that may interfere with their educational success and affect their healthy development and their life-long outcomes. This research study examined the concurrent and longitudinal…

  9. Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective.

    PubMed

    Herwig, R; Gmuender, H; Corvi, R; Bloch, K M; Brandenburg, A; Castell, J; Ceelen, L; Chesne, C; Doktorova, T Y; Jennen, D; Jennings, P; Limonciel, A; Lock, E A; McMorrow, T; Phrakonkham, P; Radford, R; Slattery, C; Stierum, R; Vilardell, M; Wittenberger, T; Yildirimman, R; Ryan, M; Rogiers, V; Kleinjans, J

    2016-09-01

    The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing. PMID:26525393

  10. Illness Uncertainty and Quality of Life of Patients with Small Renal Tumors Undergoing Watchful Waiting: A 2-year Prospective Study

    PubMed Central

    Parker, Patricia A.; Alba, Frances; Fellman, Bryan; Urbauer, Diana L.; Li, Yisheng; Karam, Jose A.; Tannir, Nizar; Jonasch, Eric; Wood, Christopher G.; Matin, Surena F.

    2013-01-01

    Background Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. Objective To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. Design, setting, and participants In 2006–2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician–patient interaction. Participants had suspected clinical stage T1–T2 disease, were aged ≥18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. Outcome measurements and statistical analysis Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System–Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. Results and limitations Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.02 cm/yr (standard deviation: 0.03). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p = 0.008); worse cancer-related QOL in physical (p = 0.001), psychosocial (p < 0.001), and medical (p = 0.034) domains; and higher distress (p < 0.001). Conclusions This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the

  11. Acoustic evidence for the development of gestural coordination in the speech of 2-year-olds: a longitudinal study.

    PubMed

    Goodell, E W; Studdert-Kennedy, M

    1993-08-01

    Studies of child phonology have often assumed that young children first master a repertoire of phonemes and then build their lexicon by forming combinations of these abstract, contrastive units. However, evidence from children's systematic errors suggests that children first build a repertoire of words as integral sequences of gestures and then gradually differentiate these sequences into their gestural and segmental components. Recently, experimental support for this position has been found in the acoustic records of the speech of 3-, 5-, and 7-year-old children, suggesting that even in older children some phonemes have not yet fully segregated as units of gestural organization and control. The present longitudinal study extends this work to younger children (22- and 32-month-olds). Results demonstrate clear differences in the duration and coordination of gestures between children and adults, and a clear shift toward the patterns of adult speakers during roughly the third year of life. Details of the child-adult differences and developmental changes vary from one aspect of an utterance to another. PMID:8377484

  12. Cardiovascular Effects of Dietary Salt Intake in Aged Healthy Cats: A 2-Year Prospective Randomized, Blinded, and Controlled Study

    PubMed Central

    Chetboul, Valérie; Reynolds, Brice Stéphane; Trehiou-Sechi, Emilie; Nguyen, Patrick; Concordet, Didier; Sampedrano, Carolina Carlos; Testault, Isabelle; Elliott, Jonathan; Abadie, Jérôme; Biourge, Vincent; Lefebvre, Hervé Pierre

    2014-01-01

    High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1±2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some

  13. Duration of untreated psychosis predicts functional and clinical outcome in children and adolescents with first-episode psychosis: a 2-year longitudinal study.

    PubMed

    Fraguas, David; Del Rey-Mejías, Angel; Moreno, Carmen; Castro-Fornieles, Josefina; Graell, Montserrat; Otero, Soraya; Gonzalez-Pinto, Ana; Moreno, Dolores; Baeza, Inmaculada; Martínez-Cengotitabengoa, Mónica; Arango, Celso; Parellada, Mara

    2014-01-01

    Longer duration of untreated psychosis (DUP) in adult patients with first-episode psychosis (FEP) has been associated with poor clinical and social outcomes. We aimed to estimate the influence of DUP on outcome at 2-year follow-up in subjects with an early-onset (less than 18 years of age) FEP of less than 6 months' duration. A total of 80 subjects (31.3% females, mean age 16.0±1.8 years) were enrolled in the study. The influence of DUP on outcome was estimated using multiple regression models (two linear models for influence of DUP on the C-GAF at 2 years and C-GAF change through the follow-up period, and a logistic model for influence of DUP on 41 PANSS remission at 2 years in schizophrenia patients (n=47)). Mean DUP was 65.3±54.7 days. Median DUP was 49.5 days. For the whole sample (n=80), DUP was the only variable significantly related to C-GAF score at 2-year follow-up (Beta=-0.13, p<0.01), while DUP and premorbid adjustment (Beta=-0.01, p<0.01; and Beta=-0.09, p=0.04, respectively) were the only variables significantly related to C-GAF change. In schizophrenia patients, DUP predicted both C-GAF score at 2 years and C-GAF change, while in patients with affective psychosis (n=22), DUP was unrelated to outcome. Lower baseline C-GAF score (OR=0.91, p<0.01) and shorter DUP (OR=0.98, p=<0.01) were the only variables that significantly predicted clinical remission in schizophrenia patients. In conclusion, longer DUP was associated with lower C-GAF at 2 years, less increase in C-GAF, and lower rates of clinical remission in early-onset FEP. Our findings support the importance of early detection programs, which help shorten DUP. PMID:24332406

  14. Sporadic community-acquired Legionnaires' disease in France: a 2-year national matched case-control study.

    PubMed

    Che, D; Campese, C; Santa-Olalla, P; Jacquier, G; Bitar, D; Bernillon, P; Desenclos, J-C

    2008-12-01

    Legionnaires' disease (LD) is an aetiology of community-acquired bacterial pneumonia in adults, with a high case-fatality ratio (CFR). We conducted a matched case-control study to identify risk factors for sporadic, community-acquired LD. Cases of sporadic, community-acquired and biologically confirmed LD, in metropolitan France from 1 September 2002 to 31 September 2004, were matched with a control subject according to age, sex, underlying illness and location of residence within 5 km. We performed a conditional logistic regression on various host-related factors and exposures. Analysis was done on 546 matched pairs. The CFR was 3.5%. Age ranged from 18-93 years (mean 57 years), with a 3.6 male:female sex ratio. Cases were more likely to have smoked with the documentation of a dose-effect relation, to have travelled with a stay in a hotel (OR 6.1, 95% CI 2.6-14.2), or to have used a wash-hand basin for personal hygiene (OR 3.5, 95% CI 1.6-7.7) than controls. Tobacco and travel have been previously described as risk factors for LD, but this is the first time that such a dose-effect for tobacco has been documented among sporadic cases. These findings will provide helpful knowledge about LD and help practitioners in identifying patients at high risk. PMID:18211725

  15. 2-year study of chemical composition of bulk deposition in a South China coastal city: comparison with East Asian cities

    SciTech Connect

    K.M. Wai; P.A. Tanner; C.W.F. Tam

    2005-09-01

    Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, Ca{sup 2+}, and NH{sub 4}{sup +} concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from the collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, Ca{sup 2+}, and NH{sub 4}{sup +}. All species concentrations show higher levels in the cold season (especially NO{sub 3}- and Ca{sup 2+}), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed. 36 refs., 3 figs., 5 tabs.

  16. 2-year study of chemical composition of bulk deposition in a south China coastal city: comparison with east Asian cities.

    PubMed

    Wai, K M; Tanner, P A; Tam, C W F

    2005-09-01

    Using the emission strengths of the precursor gases, the nature of soil in China, the ventilation power and half value rainout region length, the nss-SO42-, NO3-, Ca2+, and NH4+ concentrations, and pH of rainwater at Hong Kong and other cities of China and Japan are compared and rationalized. The chemical composition of Hong Kong bulk deposition from 1998 to 2000 is taken from our collection and analysis of 156 daily samples. The volume-weighted average (VWA) pH is 4.2 over the whole study period. Nonsea salt- (nss-) sulfate is the most abundant species in the samples, and the pH mostly depended upon the concentrations of the major species nss-SO42, NO3-, Ca2+, and NH4+. All species concentrations show higher levels in the cold season (especially NO3- and Ca2+), which indicates the dominant dilution effects in the warm season due to heavy rainfall and the influence of the continental outflow of pollutants during the cold season. For Hong Kong bulk deposition, the VWA pH is slightly lower in the cold season, and there is a slight decrease in VWA pH over the period from 1994 to 2000. The impact of acid rain in Hong Kong is briefly discussed. PMID:16190210

  17. Prognostic value of low and moderately elevated C-reactive protein in acute coronary syndrome: A 2-year follow-up study

    PubMed Central

    Lukin, Ajvor; Novak, Katarina; Polić, Stojan; Puljak, Livia

    2013-01-01

    Background The main goal of this study was to improve diagnostic and predictive value of low and moderately elevated C-reactive protein (CRP) in patients with acute coronary syndrome (ACS), related to noninvasive clinical parameters, in order to improve and prolong patient life with low or no additional costs. Material/Methods A prospective, open clinical study was conducted at the University Hospital Split, Croatia with 112 patients with ACS and low or moderately elevated CRP (<3.0 mg/L). After diagnosing ACS, data on physical activity, alcohol consumption, and functional status were recorded. Anthropometric measurements were made. Blood and urine samples were taken for analyses. Electrocardiographic, ergometric, and echocardiographic testing was performed. A total of 72 parameters were monitored at the time of hospital admission in ACS patients to analyze which ones could predict disease outcome at the end of follow-up in patients with low or moderately elevated CRP. Patients were followed up for 2 years. Results The variables that were predictive of major adverse cardiac events (MACE) within 2 years of ACS hospitalization were hemoglobin, fibrinogen, antithrombin III, cholesterol levels, brain natriuretic peptide, and microalbuminuria. ACS patients with CRP <3.0 mg/L had significantly higher risk of developing MACE within 2 years if ≥50% of the 8 key parameters were outside the reference values. Conclusions Major adverse cardiac events can be predicted in patients with acute coronary syndrome whose CRP values are low or moderately elevated. PMID:24051868

  18. Prevalence of and risk factors for persistent postoperative nonanginal pain after cardiac surgery: a 2-year prospective multicentre study

    PubMed Central

    Choinière, Manon; Watt-Watson, Judy; Victor, J. Charles; Baskett, Roger J.F.; Bussières, Jean S.; Carrier, Michel; Cogan, Jennifer; Costello, Judy; Feindel, Christopher; Guertin, Marie-Claude; Racine, Mélanie; Taillefer, Marie-Christine

    2014-01-01

    Background: Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery. Methods: We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up. Results: A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain. Interpretation: Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain. PMID:24566643

  19. A longitudinal study of Giardia duodenalis genotypes in dairy cows from birth to 2 years of age.

    PubMed

    Santín, Mónica; Trout, James M; Fayer, Ronald

    2009-05-26

    Fecal specimens were collected from 30 calves from birth to 24 months of age at a dairy farm in Maryland to determine the prevalence of Giardia duodenalis genotypes in cattle of different ages. Fecal samples were subjected to density gradient centrifugation to remove debris and concentrate cysts. Specimens were analyzed by immunofluorescence microscopy and polymerase chain reaction (PCR). All PCR positive specimens were sequenced using the SSU-rRNA gene of Giardia. All 30 calves shed G. duodenalis cysts at some time during the study. Of 990 specimens, 312 were positive for G. duodenalis (31.5%). The highest prevalence of infection occurred at weeks 4 and 5 of age with 25 out of 30 calves shedding cysts at those sampling times. Overall, pre-weaned calves (<8 weeks of age) exhibited the highest prevalence (60.8%), followed by post-weaned calves (3-12 months of age) (32.1%) and heifers (12-24 months of age) (11.4%). Sequence analysis of the 312 PCR-positive samples revealed the presence of both Assemblages A and E, G. duodenalis, with cumulative prevalences of 70% and 100%, respectively. Assemblage A was not detected in pre-weaned calves, but was detected in 6.9% and 4.7% of post-weaned calves and heifers, respectively. These data indicate not only that calves are infected with both Assemblages A and E simultaneously, but also that infections with zoonotic Assemblage A, G. duodenalis are more common than previously reported. Thus, calves appear to be a more significant reservoir of human infectious G. duodenalis than previous data have suggested. PMID:19264407

  20. Prospective Study Evaluating Postoperative Radiotherapy Plus 2-Year Androgen Suppression for Post-Radical Prostatectomy Patients With Pathologic T3 Disease and/or Positive Surgical Margins

    SciTech Connect

    Choo, Richard Danjoux, Cyril; Gardner, Sandra; Morton, Gerard; Szumacher, Ewa; Loblaw, D. Andrew; Cheung, Patrick; Pearse, Maria

    2009-10-01

    Purpose: To determine the efficacy of a combined approach of postoperative radiotherapy (RT) plus 2-year androgen suppression (AS) for patients with pathologic T3 disease (pT3) and/or positive surgical margins (PSM) after radical prostatectomy (RP). Methods and Materials: A total of 78 patients with pT3 and/or PSM after RP were treated with RT plus 2-year AS, as per a pilot, prospective study. Androgen suppression started within 1 month after the completion of RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate, including freedom from prostate-specific antigen (PSA) relapse, was estimated using the Kaplan-Meier method. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Prostate-specific antigen relapse was defined as a PSA rise above 0.2 ng/mL, with two consecutive increases over a minimum of 3 months. Results: The median age was 61 years at the time of RP. The median interval between RP and postoperative RT was 4.2 months. Forty-nine patients had undetectable PSA (<0.2 ng/mL), and 29 had persistently detectable postoperative PSA at the time of the protocol treatment. Median follow-up from RT was 6.4 years. Relapse-free rates at 5 and 7 years were 94.4% and 86.3%, respectively. Survival rates were 96% at 5 years and 93.1% at 7 years. On Cox regression analysis, persistently detectable postoperative PSA and pT3b-T4 were significant predictors for relapse. Conclusion: The combined treatment of postoperative RT plus 2-year AS yielded encouraging results for patients with pT3 and/or PSM and warrants a confirmatory study.

  1. A combined dietary chronic toxicity and two-year carcinogenicity study of (2R,4R)-monatin salt in Sprague-Dawley rats.

    PubMed

    Brathwaite, Witty A; Crincoli, Christine M; Eapen, Alex K; Rihner, Marisa O; Nikiforov, Andrey I; Remick, Amera K

    2016-05-01

    In a combined chronic toxicity/carcinogenicity study, groups of Crl:CD(SD) rats were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm (2R,4R)-monatin salt (hereafter "R,R-monatin") in the diet for up to one year in the chronic toxicity phase and up to two years in the carcinogenicity phase. There were no adverse effects on survival, incidence of palpable masses, neoplasms, organ weights, or ophthalmic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups generally throughout the study, which were most likely a result of caloric dilution of the test diets. Effects of long-term R,R-monatin ingestion by rats were predominantly focused on the urinary system (i.e., clinical pathology alterations indicative of electrolyte and pH imbalances, increased incidence of renal calculi, mineralization and bone hyperostosis, and increased severity of chronic progressive nephropathy). The no-observed-adverse-effect level (NOAEL) for R,R-monatin from the chronic toxicity phase was 20,000 ppm (equivalent to an exposure level of 1080 mg/kg bw/day for males and 1425 mg/kg/day for females) and from the carcinogenicity phase was 5000 ppm (equivalent to an exposure level of 238 and 302 mg/kg bw/day for males and females, respectively). PMID:26747978

  2. Cementless anatomical prosthesis for the treatment of 3-part and 4-part proximal humerus fractures: cadaver study and prospective clinical study with minimum 2 years followup

    PubMed Central

    Obert, Laurent; Saadnia, Rachid; Loisel, François; Uhring, Julien; Adam, Antoine; Rochet, Séverin; Clappaz, Pascal; Lascar, Tristan

    2016-01-01

    Introduction: The purpose of this study was to evaluate the functional and radiological outcomes of a cementless, trauma-specific locked stem for 3- and 4-part proximal humeral fractures. Materials and methods: This study consisted of two parts: a cadaver study with 22 shoulders and a multicenter prospective clinical study of 23 fracture patients evaluated at least 2 years after treatment. In the cadaver study, the locked stem (HumelockTM, FX Solutions) and its instrumentation were evaluated. In the clinical study, five senior surgeons at four different hospitals performed the surgical procedures. An independent surgeon evaluated the patients using clinical (Constant score, QuickDASH) and radiological (X-rays, CT scans) outcome measures. Results: The cadaver study allowed us to validate the height landmarks relative to the pectoralis major tendon. In the clinical study, at the review, abduction was 95° (60–160), forward flexion was 108° (70–160), external rotation (elbow at body) was 34° (0–55), the QuickDASH was 31 (4.5–59), the overall Constant score was 54 (27–75), and the weighted Constant score was 76 (31.5–109). Discussion: This preliminary study of hemiarthroplasty (HA) with a locked stem found results that were at least equivalent to published series. As all patients had at least a 2-year follow-up, integration of the locked stem did not cause any specific complications. These results suggest that it is possible to avoid using cement when hemiarthroplasty is performed for the humeral stem. This implant makes height adjustment and transosseous suturing of the tuberosities more reproducible. PMID:27194107

  3. Parental Estimation of Their Child's Increased Type 1 Diabetes Risk During the First 2 Years of Participation in an International Observational Study: Results From the TEDDY study.

    PubMed

    Swartling, Ulrica; Lynch, Kristian; Smith, Laura; Johnson, Suzanne Bennett

    2016-04-01

    This study assessed mothers' and fathers' perception of their child's risk of getting type 1 diabetes (T1D) during the first 2 years of their participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study. TEDDY parents were informed of their child's increased genetic risk for T1D at study inception. Parent perception of the child's risk was assessed at 3, 6, 15, and 27 months of age. In families with no history of T1D, underestimation of the child's T1D risk was common in mothers (>38%) and more so in fathers (>50%). The analyses indicated that parental education, country of residence, family history of T1D, household crowding, ethnic minority status, and beliefs that the child's T1D risk can be reduced were factors associated with parental risk perception accuracy. Even when given extensive information about their child's T1D risk, parents often fail to accurately grasp the information provided. This is particularly true for fathers, families from low socioeconomic backgrounds, and those with no family history of T1D. It is important to develop improved tools for risk communication tailored to individual family needs. PMID:27241873

  4. Joint unloading implant modifies subchondral bone trabecular structure in medial knee osteoarthritis: 2-year outcomes of a pilot study using fractal signature analysis

    PubMed Central

    Miller, Larry E; Sode, Miki; Fuerst, Thomas; Block, Jon E

    2015-01-01

    Background Knee osteoarthritis (OA) is largely attributable to chronic excessive and aberrant joint loading. The purpose of this pilot study was to quantify radiographic changes in subchondral bone after treatment with a minimally invasive joint unloading implant (KineSpring® Knee Implant System). Methods Nine patients with unilateral medial knee OA resistant to nonsurgical therapy were treated with the KineSpring System and followed for 2 years. Main outcomes included Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, and stiffness subscores and independent core laboratory determinations of joint space width and fractal signature of the tibial cortex. Results WOMAC scores, on average, improved by 92% for pain, 91% for function, and 79% for stiffness over the 2-year follow-up period. Joint space width in the medial compartment of the treated knee significantly increased from 0.9 mm at baseline to 3.1 mm at 2 years; joint space width in the medial compartment of the untreated knee was unchanged. Fractal signatures of the vertically oriented trabeculae in the medial compartment decreased by 2.8% in the treated knee and increased by 2.1% in the untreated knee over 2 years. No statistically significant fractal signature changes were observed in the horizontally oriented trabeculae in the medial compartment or in the horizontal or vertical trabeculae of the lateral compartment in the treated knee. Conclusion Preliminary evidence suggests that the KineSpring System may modify knee OA disease progression by increasing joint space width and improving subchondral bone trabecular integrity, thereby reducing pain and improving joint function. PMID:25670891

  5. Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study.

    PubMed

    Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuuki; Moriwaki, Norichika; Sekijima, Masaru; Otsuka, Masanori; Yakabe, Yoshikuni; Miyaura, Hideki; Saito, Koichi; Sumida, Kayo; Shirai, Tomoyuki

    2006-12-15

    Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as "carcinogenic", and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as "non-carcinogenic"; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as "carcinogenic", and 4-AAF, 2,6-DAT, and 1-NP as "non-carcinogenic". After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a "carcinogenic" branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity. PMID:17070881

  6. A study of the efficacy and safety of albendazole (Zentel) in the treatment of intestinal helmenthiasis in Kenyan children less than 2 years of age.

    PubMed

    Pamba, H O; Bwibo, N O; Chunge, C N; Estambale, B B

    1989-03-01

    One hundred children comprising of 57 males and 43 females aged between 8 and 24 months entered the study. 46 children had single and 54 children had multiple helminth infections. All children received albendazole 200 mg (10 ml) suspension as a single dose. Albendazole proved very effective and safe in the treatment of single and multiple helminth infections in children under 2 years of age, achieving cure rates of 100% in both Ascaris lumbricoides and Necator americanus respectively, 83% in Trichuris trichiura and 66% in Hymenolepis nana. Treatment of polyparasitism appears to be of benefit in improving nutritional status using haemoglobin concentrations as an index. PMID:2591328

  7. Toxicity and Carcinogenicity of Dichlorodiphenyltrichloroethane (DDT)

    PubMed Central

    Harada, Takanori; Takeda, Makio; Kojima, Sayuri; Tomiyama, Naruto

    2016-01-01

    Dichlorodiphenyltrichloroethane (DDT) is still used in certain areas of tropics and subtropics to control malaria and other insect-transmitted diseases. DDT and its metabolites have been extensively studied for their toxicity and carcinogenicity in animals and humans and shown to have an endocrine disrupting potential affecting reproductive system although the effects may vary among animal species in correlation with exposure levels. Epidemiologic studies revealed either positive or negative associations between exposure to DDT and tumor development, but there has been no clear evidence that DDT causes cancer in humans. In experimental animals, tumor induction by DDT has been shown in the liver, lung, and adrenals. The mechanisms of hepatic tumor development by DDT have been studied in rats and mice. DDT is known as a non-genotoxic hepatocarcinogen and has been shown to induce microsomal enzymes through activation of constitutive androstane receptor (CAR) and to inhibit gap junctional intercellular communication (GJIC) in the rodent liver. The results from our previously conducted 4-week and 2-year feeding studies of p,p′-DDT in F344 rats indicate that DDT may induce hepatocellular eosinophilic foci as a result of oxidative DNA damage and leads them to hepatic neoplasia in combination with its mitogenic activity and inhibitory effect on GJIC. Oxidative stress could be a key factor in hepatocarcinogenesis by DDT. PMID:26977256

  8. Dietary Carcinogens and Anticarcinogens.

    ERIC Educational Resources Information Center

    Ames, Bruce N.

    1983-01-01

    Describes 16 mutagens/carcinogens found in plant food and coffee as well as several anticarcinogens also found in such food. Speculates on relevant biochemical mechanisms, particularly the role of oxygen radicals and their inhibitors in the fat/cancer relationship, promotion, anticarcinogenesis, and aging. (JN)

  9. CPDB: Carcinogenic Potency Database.

    PubMed

    Fitzpatrick, Roberta Bronson

    2008-01-01

    The Carcinogenic Potency Database reports analyses of animal cancer tests on 1,547 chemicals. These tests are used in support of cancer risk assessments for humans. Results are searchable and are made available via the National Library of Medicine's (NLM) TOXNET system. This column will provide background information on the database, as well as present search basics. PMID:19042710

  10. Effect of Workplace Noise on Hearing Ability in Tile and Ceramic Industry Workers in Iran: A 2-Year Follow-Up Study

    PubMed Central

    Mirmohammadi, Seyyed Jalil; Mehrparvar, Amir Houshang; Mollasadeghi, Abolfazl

    2013-01-01

    Introduction. Noise as a common physical hazard may lead to noise-induced hearing loss, an irreversible but preventable disorder. Annual audiometric evaluations help detect changes in hearing status before clinically significant hearing loss develops. This study was designed to track hearing threshold changes during 2-year follow-up among tile and ceramic workers. Methods. This follow-up study was conducted on 555 workers (totally 1110 ears). Subjects were divided into four groups according to the level of noise exposure. Hearing threshold in conventional audiometric frequencies was measured and standard threshold shift was calculated for each ear. Results. Hearing threshold was increased during 2 years of follow-up. Increased hearing threshold was most frequently observed at 4000, 6000, and 3000 Hz. Standard threshold shift was observed in 13 (2.34%), 49 (8.83%), 22 (3.96%), and 63 (11.35%) subjects in the first and second years of follow-up in the right and left ears, respectively. Conclusions. This study has documented a high incidence of noise-induced hearing loss in tile and ceramic workers that would put stress on the importance of using hearing protection devices. PMID:24453922

  11. Impaired visual fixation at age 2 years in children born before the 28th week of gestation. Antecedents and correlates in the multi-center ELGAN Study

    PubMed Central

    Phadke, Anuradha; Msall, Michael E; Droste, Patrick; Allred, Elizabeth N; O'Shea, T. Michael; Kuban, Karl; Dammann, Olaf; Leviton, Alan

    2014-01-01

    Background Very little is known about the prevalence, antecedents and correlates of impaired visual fixation in former very preterm newborns. Methods In the multi-center ELGAN Study sample of 1057 infants born before the 28th week of gestation who had a developmental assessment at 2 years corrected age, we identified 73 who were unable to follow an object across the midline. We compared them to the 984 infants who could follow an object across the midline. Results In this sample of very preterm newborns, those who had impaired visual fixation were much more likely than those without impaired visual fixation to have been born after the shortest of gestations (odds ratio = 3.2; 99% confidence interval =1.4, 7.5) and exposed to maternal aspirin (OR: 5.2; 99% CI: 2.2, 12). They were also more likely than their peers to have had prethreshold ROP (OR: 4.1; 99% CI: 1.8, 9.0). At age 2 years, the children with impaired fixation were more likely than others to be unable to walk (even with assistance) (OR: 7.5; 99% CI: 2.2, 26) and have a Mental Development Index more than 3 standard deviations below the mean of a normative sample (OR:3.6; 99% CI: 1.4, 8.2). Conclusion Risk factors for brain and retinal damage, such as very low gestational age, appear to be risk factors for impaired visual fixation. This inference is further supported by the co-occurrence at age 2 years of impaired visual fixation, inability to walk, and a very low Mental Development Index PMID:24938138

  12. Flare, Persistently Active Disease, and Serologically Active Clinically Quiescent Disease in Systemic Lupus Erythematosus: A 2-Year Follow-Up Study

    PubMed Central

    Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Miranda, Francesca; Truglia, Simona; Massaro, Laura; Pacucci, Viviana Antonella; Conti, Virginia; Bartosiewicz, Izabella; Spinelli, Francesca Romana; Alessandri, Cristiano; Valesini, Guido

    2012-01-01

    Objective Several indices have been proposed to assess disease activity in patients with Systemic Lupus Erythematosus (SLE). Recent studies have showed a prevalence of flare between 28–35.3%, persistently active disease (PAD) between 46%–52% and serologically active clinically quiescent (SACQ) disease ranging from 6 to 15%. Our goal was to evaluate the flare, PAD and SACQ rate incidence in a cohort of SLE patients over a 2-year follow-up. Methods We evaluated 394 SLE patients. Flare was defined as an increase in SLEDAI-2K score of ≥4 from the previous visit; PAD was defined as a SLEDAI-2K score of ≥4, on >2 consecutive visits; SACQ was defined as at least a 2-year period without clinical activity and with persistent serologic activity. Results Among the 95 patients eligible for the analysis in 2009, 7 (7.3%) had ≥1 flare episode, whereas 9 (9.4%) had PAD. Similarly, among the 118 patients selected for the analysis in 2010, 6 (5%) had ≥1 flare episode, whereas 16 (13.5%) had PAD. Only 1/45 patient (2.2%) showed SACQ during the follow-up. Conclusion We showed a low incidence of flare, PAD and SACQ in Italian SLE patients compared with previous studies which could be partly explained by ethnic differences. PMID:23029327

  13. Studies on the local and systemic carcinogenicity of topically applied smoke condensate from a substitute smoking material.

    PubMed Central

    Clapp, M. J.; Conning, D. M.; Wilson, J.

    1977-01-01

    The topical carcinogenicity to mouse skin of smoke condensates obtained from a tobacco substitute (NSM), alone or in combination with tobacco, has been compared with condensate from tobacco and with acetone, the solvent used. Sixteen different types of cigarette were used to make the condensates, and the age-standardized results have been analysed according to the Weibull distribution model. The results show that NSM condensate has less than 25% of the potency of tobacco condensate (37% at 95% upper confidence limit), and that condensates from blends of NSM and tobacco are similarly reduced in activity. General pathology analysis failed to reveal abnormalities due to NSM. PMID:851510

  14. TOXICITY AND CARCINOGENICITY STUDIES OF 4-METHYLIMIDAZOLE IN F344/N RATS AND B6C3F1 MICE

    PubMed Central

    Chan, P.C.; Hills, G. D; Kissling, G.E.; Nyska, A

    2008-01-01

    4-Methylimidazole (4MI) is used in the manufacture of pharmaceuticals, photographic chemicals, dyes and pigments, cleaning and agricultural chemicals, and rubber. It has been identified as a by-product of fermentation in foods and has been detected in mainstream and side stream tobacco smoke. 4MI was studied because of its high potential for human exposure. Groups of 50 male and 50 female F344/N rats were fed diets containing 0-, 625-, 1,250-, or 2,500-ppm 4MI (males) or 0-, 1,250-, 2,500-, or 5,000-ppm 4MI (females) for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 30, 55, or 115 mg 4MI/kg body weight to males and 60, 120, or 250 mg 4MI/kg to females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males in the 1,250- and 2,500-ppm groups and females in the 2,500- and 5,000-ppm groups were less than those of the control groups throughout the study. Feed consumption by 5,000-ppm females was less than that by the controls. Clonic seizures, excitability, hyperactivity, and impaired gait were observed primarily in 2,500- and 5,000-ppm females. The incidence of mononuclear cell leukemia in the 5,000-ppm females was significantly greater than that in the controls. The incidences of hepatic histiocytosis, chronic inflammation, and focal fatty change were significantly increased in all exposed groups of male and female rats. The incidences of hepatocellular eosinophilic and mixed cell foci were significantly increased in 2,500-ppm males and 5,000-ppm females. Groups of 50 male and 50 female B6C3F1 mice were fed diets containing 0-, 312-, 625-, or 1,250-ppm 4MI for 106 weeks. Based on the food consumption the calculated average daily doses were approximately 40, 80, or 170 mg 4MI/kg body weight to males and females. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of males and females in the 1

  15. Thresholds of carcinogenicity of flavors.

    PubMed

    Waddell, William J

    2002-08-01

    Fifteen compounds approved by the FEMA (Flavor and Extract Manufacturers Association) expert panel as GRAS (Generally Recognized As Safe) and structurally related compounds have been reported to be carcinogenic in rodent studies. The dose response of the 15 compounds in these studies was scrutinized by attempting to plot the percentage of animals with tumors against the dose of the compound on a logarithmic scale in molecules of compound per kg per day (the Rozman scale). Four compounds had either no or an inverse dose response: benzaldehyde, furfural, 3,4-dihydroxycoumarin, and gamma-buterolactone. Three had a response at one dose only: anethole, estragole (2 studies), and isophorone. Obviously, a dose-response curve could not be generated for these 7 compounds. Four compounds had an increasing response at two doses (benzyl acetate, cinnamyl anthranilate, ethyl acrylate, and estragole); three compounds had increasing responses at three doses (citral, 2,4-hexadienal, and pyridine); one compound had increasing responses at four doses (methyl eugenol). The three compounds with three doses fit a linear plot with a correlation coefficient of at least 0.9; the four doses in male rats of methyl eugenol fit a linear plot with a correlation coefficient of 0.999983. The intercept at zero percentage tumors of these linear fits was at least several orders of magnitude greater than the estimated daily dose of these flavoring agents to individuals in the United States. This is interpreted to indicate that these flavoring agents have a clear threshold for carcinogenicity in animals that is well above the levels currently approved for use in foods; consequently, these animal studies should not be a cause for concern for carcinogenicity of these compounds in humans. Rather, the animal studies should be viewed as providing evidence for the safety of these compounds at current levels of human exposure. PMID:12151622

  16. The carcinogenicity of chrysotile asbestos

    SciTech Connect

    Harington, J.S. )

    1991-12-31

    In in vitro test systems, chrysotile is markedly toxic, causes chromosomal aberrations, and is capable of inducing morphological and preneoplastic transformation. In carefully designed animal experiments, chrysotile produces lung cancer and mesothelioma as effectively as do the amphiboles tested. Human population studies do not refute these experimental results. Chrysotile asbestos is carcinogenic to humans, especially for the induction of lung cancer and mesothelioma in exposed populations. For cancers of other sites, with the exception of laryngeal and possibly gastrointestinal cancer, the evidence for association with exposure to all forms of asbestos, including chrysotile, is not yet adequate for evaluation.48 references.

  17. CCL2, CCL18 and sIL-4R in renal, meningeal and pulmonary TB; a 2 year study of patients and contacts.

    PubMed

    Mendez, Armando; Hernandez-Pando, Rogelio; Contreras, Salvador; Aguilar, Diana; Rook, Graham A W

    2011-03-01

    The role of Th2 cytokines and Th2-associated chemokines in tuberculosis (TB) remains controversial, though in Mexico a polymorphism causing increased production of CCL2 is a risk factor. We studied levels of the Th2-associated chemokines CCL2 and CCL18, circulating soluble IL-4 receptors (sIL-4R), IL-4 and the inhibitory splice variant of IL-4 (IL-4δ2) in a cohort of patients with pulmonary TB and their healthy contacts. These were followed for 2 years during which time 10 contacts developed pulmonary TB. Results were compared with measurements made in renal and meningeal TB, and in disease controls with bacterial pneumonias or Dengue fever that have large Th2 components. In these disease controls both chemokines were significantly raised. They were also very significantly raised in all forms of TB, irrespective of age or disease site. Levels of CCL18 were raised least in meningeal TB, and most in pulmonary patients with long histories, when levels were similar to those in disease controls. Levels of CCL2, although also raised in all three forms of TB, were negatively correlated with CCL18. We found that levels of sIL-4R were strikingly reduced in all forms of TB, particularly meningeal. Contacts who progressed could not be distinguished from contacts who remained healthy at 2 years in terms of IL-4, sIL-4R, CCL2 or CCL18. However contacts had raised expression of IL-4δ2 as previously found. These results indicate vigorous and previously unrecorded activity within the Th2 axis, and further investigation is warranted. PMID:21251883

  18. Changes in the frequency of benign focal spikes accompany changes in central information processing speed: a prospective 2-year follow-up study.

    PubMed

    Ebus, S C M; IJff, D M; den Boer, J T; van Hall, M J H; Klinkenberg, S; van der Does, A; Boon, P J; Arends, J B A M; Aldenkamp, A P

    2015-02-01

    We prospectively examined whether changes in the frequency of benign focal spikes accompany changes in cognition. Twenty-six children with benign focal spikes (19 with Rolandic epilepsy) and learning difficulties were examined with repeated 24-hour EEG recordings, three cognitive tests on central information processing speed (CIPS), and questionnaires on cognition and behavior at baseline, 6months, and 2years. Antiepileptic drug changes were allowed when estimated necessary by the treating physician. At baseline, a lower CIPS was correlated with a higher frequency of diurnal interictal epileptiform discharges (IEDs) and with worse academic achievement. At follow-up, there was a significant correlation between changes in CIPS and EEG changes in wakefulness (in the same direction) when the EEG outcome was dichotomized in IED frequency "increased" or "not increased". Behavioral problems were more often observed in patients with higher frequency of IEDs in sleep at baseline and in those with ongoing IEDs compared with those with EEG remission (without or with sporadic IEDs in the recording) at the end of the study period. No changes were observed in the results of the questionnaires. A lower diurnal IED frequency at baseline, lack of serial IEDs, and occurrence of only unilateral IEDs were correlated with a higher chance of EEG remission at 2-year follow-up. Electroencephalography remission could not be predicted from other epilepsy variables except from seizure freedom in the last six months. Our results confirm the nonbenign character of 'benign' focal spikes. Whether an early and stable EEG remission can be achieved through antiepileptic treatment and whether this is of benefit for cognitive development should be examined in prospective placebo-controlled randomized trials. PMID:25546731

  19. Determinants of “return to work in good health” among workers with back pain who consult in primary care settings: a 2-year prospective study

    PubMed Central

    Bourbonnais, Renée; Frémont, Pierre; Rossignol, Michel; Stock, Susan R.; Nouwen, Arie; Larocque, Isabelle; Demers, Eric

    2006-01-01

    Many factors have been linked to return to work after a back pain episode, but our understanding of this phenomenon is limited and cross-sectional dichotomous indices of return to work are not valid measures of this construct. To describe the course of “return to work in good health” (RWGH—a composite index of back pain outcome) among workers who consulted in primary care settings for back pain and identify its determinants, a 2-year prospective study was conducted. Subjects (n = 1,007, 68.4%) were workers who consulted in primary care settings of the Quebec City area for a nonspecific back pain. They completed five telephone interviews over 2 years (follow-up = 86%). Analyses linking baseline variables with 2-year outcome were conducted with polytomous logistic regression. The proportion of “success” in RWGH increased from 18% at 6 weeks to 57% at 2 years. In women, persistent pain, pain radiating to extremities, increasing job seniority, not having a unionized job, feeling that the physician did listen carefully and increasing fear-avoidance beliefs towards work and activity were determinants of “failure” in RWGH. In men, decreasing age, cigarette smoking, poor self-reported health status, pain in the thoracic area, previous back surgeries, a non-compensated injury, high pain levels, belief that job is below qualifications, likelihood of losing job, job status, satisfaction with health services and fear-avoidance beliefs towards work were all significant. RWGH among workers with back pain receives multiple influences, especially among men. In both genders, however, fear-avoidance beliefs about work are associated with failure and high self-efficacy is associated with success. PMID:16868783

  20. Social Development:: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Social Development: 2 Year Olds Page Content Article Body By nature, ... probably are acting the same way. At age two, children view the world almost exclusively through their ...

  1. Language Development: 2 Year Olds

    MedlinePlus

    ... Stages Listen Español Text Size Email Print Share Language Development: 2 Year Olds Page Content Article Body ... Pay attention to how he also is using language to describe ideas and information and to express ...

  2. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study)

    PubMed Central

    Perez-Saldivar, Maria Luisa; Ortega-Alvarez, Manuel Carlos; Fajardo-Gutierrez, Arturo; Bernaldez-Rios, Roberto; del Campo-Martinez, Maria de los Angeles; Medina-Sanson, Aurora; Palomo-Colli, Miguel Angel; Paredes-Aguilera, Rogelio; Martínez-Avalos, Armando; Borja-Aburto, Victor Hugo; Rodriguez-Rivera, Maria de Jesus; Vargas-Garcia, Victor Manuel; Zarco-Contreras, Jesus; Flores-Lujano, Janet; Mejia-Arangure, Juan Manuel

    2008-01-01

    Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL) in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR) of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s). In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI) was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an expert's opinion. Results The

  3. Evaluation of the potential carcinogenicity of daunomycin. Final report

    SciTech Connect

    Not Available

    1988-06-01

    Daunomycin is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is No Data. Data available are inadequate for calculating a potency factor (F) and no quantitative inferences can be made. Daunomycin is, therefore, assigned to the median potency factor range and placed in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, daunomycin is assigned a MEDIUM hazard ranking for the purposes of RQ adjustment.

  4. Comparative morphological studies on the carcinogenic effect of 7,12-dimethylbenz(A)anthracene (DMBA) in normal or intrasplenic ovarian tissue of C3H mice.

    PubMed Central

    Hilfrich, J.

    1975-01-01

    A single intravenous injection of 100 mg/kg body weight (b.w.) of 7, 12 dimethylbenz(a)anthracene (DMBA) induces a high percentage of ovarian granulosa cell tumours in C3H mice. After implantation of ovarian tissue into the spleen of gonadectomized female C3H mice similar tumours were found, resulting from an over-stimulation by pituitary gonadotrophins. In the present study the tumour development in intrasplenic ovarian tissue was observed after an additional single intravenous application of 100 mg/kg b.w. DMBA. It was found that the induction of granulosa cell tumours did not seem to be affected by the carcinogen injection whether 12 weeks before or 12 weeks after ovarian tissue was implanted into the spleen. The morphology of these neoplasms corresponds to the DMBA induced granulosa cell tumours in orthotopic ovaries. A direct carcinogenic effect of DMBA on ovarian cells in mice could not be demonstrated but there are indications that the additional DMBA application accelerated the destruction of the oocytes, which might result in a more rapid intrasplenic tumour induction. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:813756

  5. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    NASA Astrophysics Data System (ADS)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

  6. Plantar Pressure Changes and Correlating Risk Factors in Chinese Patients with Type 2 Diabetes: Preliminary 2-year Results of a Prospective Study

    PubMed Central

    Qiu, Xuan; Tian, De-Hu; Han, Chang-Ling; Chen, Wei; Wang, Zhan-Jian; Mu, Zhen-Yun; Liu, Kuan-Zhi

    2015-01-01

    Background: Plantar pressure serves as a key factor for predicting ulceration in the feet of diabetes patients. We designed this study to analyze plantar pressure changes and correlating risk factors in Chinese patients with type 2 diabetes. Methods: We recruited 65 patients with type 2 diabetes. They were invited to participate in the second wave 2 years later. The patients completed identical examinations at the baseline point and 2 years later. We obtained maximum force, maximum pressure, impulse, pressure-time integral, and loading rate values from 10 foot regions. We collected data on six history-based variables, six anthropometric variables, and four metabolic variables of the patients. Results: Over the course of the study, significant plantar pressure increases in some forefoot portions were identified (P < 0.05), especially in the second to forth metatarsal heads. Decreases in heel impulse and pressure-time integral levels were also found (P < 0.05). Plantar pressure parameters increased with body mass index (BMI) levels. Hemoglobin A1c (HbA1c) changes were positively correlated with maximum force (β = 0.364, P = 0.001) and maximum pressure (β = 0.366, P = 0.002) changes in the first metatarsal head. Cholesterol changes were positively correlated with impulse changes in the lateral portion of the heel (β = 0.179, P = 0.072) and pressure-time integral changes in the second metatarsal head (β = 0.236, P = 0.020). Ankle-brachial index (ABI) changes were positively correlated with maximum force changes in the first metatarsal head (β = 0.137, P = 0.048). Neuropathy symptom score (NSS) and common peroneal nerve sensory nerve conduction velocity (SCV) changes were positively correlated with some plantar pressure changes. In addition, plantar pressure changes had a correlation with the appearance of infections, blisters (β = 0.244, P = 0.014), and calluses over the course of the study. Conclusions: We should pay attention to the BMI, HbA1c, cholesterol, ABI

  7. Carcinogenic, teratogenic, and mutagenic effects of arsenic.

    PubMed Central

    Bencko, V

    1977-01-01

    This review outlines briefly the history and present status of the problem of carcinogenic, teratogenic and mutagenic effects of arsenic. Discrepancies between clinical observations and positive results of epidemiological studies and the experimental induction of cancer by arsenic are discussed. The present knowledge of the mechanism of teratogenic and mutagenic effects of arsenic is analyzed. The growing importance of arsenic as an environmental pollutant is demonstrated. Continuation of throughly organized epidemiological studies in regions with excessive arsenic exposure of the population and standardization of an epidemiological approach to this problem on an international basis are recommended. New approaches in experimental studies of the carcinogenicity of arsenic in combination with other known or suspected carcinogens are recommended as well. PMID:908296

  8. An FDA overview of rodent carcinogenicity studies of angiotensin II AT-1 receptor blockers: pulmonary adenomas and carcinomas.

    PubMed

    Link, William T; De Felice, Albert

    2014-11-01

    Sipahi et al. (2010) performed a meta-analysis of 5 clinical trials (n=68,402) of 3 Angiotensin II (AngII) receptor subtype AT-1 blockers (ARBs) in cardiovascular disease. It revealed excess new lung cancer diagnoses in the cohorts treated with an ARB and background therapy (0.9% vs. 0.7% in non-ARB control; RR: 1.25; CI: 1.05-1.49; p=0.01). The FDA responded with a larger meta-analysis of 31 clinical trials (n=155,816) of ARBs that found no evidence of any excess of site-specific cancer (lung, breast, prostate), solid/skin cancer or cancer death (FDA safety communication, 3 June 2011). The FDA then re-visited the 19 rodent carcinogenicity assays of 9 ARBs, starting with those for Losartan in 1994, for any evidence of dosage-related lung tumorigenicity in this class. Assays were performed in 5 strains of rats and 5 strains of wild-type and transgenic mice per protocols and dosages sanctioned by FDA's executive carcinogenicity assessment committee (eCAC). Duration was lifetime except for 26-week assays of azilsartan and olmesartan in transgenic Tg rasH2 mice, and an assay of olmesartan in p53(+/-) transgenic mice. The dosages provided exposures approximating, and in most cases up to 20-300times greater than, that in patients. Depending on strain, up to 35% of untreated mice spontaneously developed lung tumors. Regression analysis of placebo-corrected mouse lung tumor incidence collapsed across strains, gender, and ARBs vs. multiples of human exposure revealed no excess lung neoplasia. The R(2) of <0.001 reflected the virtually identical number of treated cohorts with more tumors than its control cohort vs. those with less. Regardless of strain, both control and medicated rats were essentially devoid of lung tumors in the lifetime trials. Accordingly, there was neither promotion of background lung tumors in the mouse, nor initiation of de novo lung tumors in the rat. The negative lung findings in the mouse Tg rasH2 strain are also noteworthy given that, historically

  9. Bacterial community shift is induced by dynamic environmental parameters in a changing coastal ecosystem (northern Adriatic, northeastern Mediterranean Sea)--a 2-year time-series study.

    PubMed

    Tinta, T; Vojvoda, J; Mozetič, P; Talaber, I; Vodopivec, M; Malfatti, F; Turk, V

    2015-10-01

    The potential link between the microbial dynamics and the environmental parameters was investigated in a semi-enclosed and highly dynamic coastal system (Gulf of Trieste, northern Adriatic Sea, NE Mediterranean Sea). Our comprehensive 2-year time-series study showed that despite the shallowness of this area, there was a significant difference between the surface and the bottom bacterial community structure. The bottom bacterial community was more diverse than the surface one and influenced by sediment re-suspension. The surface seawater temperature had a profound effect on bacterial productivity, while the bacterial community structure was more affected by freshwater-borne nutrients and phytoplankton blooms. Phytoplankton blooms caused an increase of Gammaproteobacteria (Alteromonadaceae, SAR86 and Vibrionaceae) and shift in dominance from SAR11 to Rhodobacteraceae taxon at the surface. Our results propose the importance of the water mass movements as drivers of freshwater-borne nutrients and of allochthonous microbial taxa. This study emphasizes the prediction power based on association networks analyses that are fed with long-term measurements of microbial and environmental parameters. These interaction maps offer valuable insights into the response of marine ecosystem to climate- and anthropogenic-driven stressors. PMID:24903068

  10. Influence of Anti-TNF and Disease Modifying Antirheumatic Drugs Therapy on Pulmonary Forced Vital Capacity Associated to Ankylosing Spondylitis: A 2-Year Follow-Up Observational Study

    PubMed Central

    Rocha-Muñoz, Alberto Daniel; Brambila-Tapia, Aniel Jessica Leticia; Zavala-Cerna, María Guadalupe; Vásquez-Jiménez, José Clemente; De la Cerda-Trujillo, Liliana Faviola; Vázquez-Del Mercado, Mónica; Rodriguez-Jimenez, Norma Alejandra; Díaz-Rizo, Valeria; Díaz-González, Viviana; Cardona-Muñoz, Ernesto German; Dávalos-Rodríguez, Ingrid Patricia; Salazar-Paramo, Mario; Gamez-Nava, Jorge Ivan; Nava-Zavala, Arnulfo Hernan; Gonzalez-Lopez, Laura

    2015-01-01

    Objective. To evaluate the effect of anti-TNF agents plus synthetic disease modifying antirheumatic drugs (DMARDs) versus DMARDs alone for ankylosing spondylitis (AS) with reduced pulmonary function vital capacity (FVC%). Methods. In an observational study, we included AS who had FVC% <80% at baseline. Twenty patients were taking DMARDs and 16 received anti-TNF + DMARDs. Outcome measures: changes in FVC%, BASDAI, BASFI, 6-minute walk test (6MWT), Borg scale after 6MWT, and St. George's Respiratory Questionnaire at 24 months. Results. Both DMARDs and anti-TNF + DMARDs groups had similar baseline values in FVC%. Significant improvement was achieved with anti-TNF + DMARDs in FVC%, at 24 months, when compared to DMARDs alone (P = 0.04). Similarly, patients in anti-TNF + DMARDs group had greater improvement in BASDAI, BASFI, Borg scale, and 6MWT when compared to DMARDs alone. After 2 years of follow-up, 14/16 (87.5%) in the anti-TNF + DMARDs group achieved the primary outcome: FVC% ≥80%, compared with 11/20 (55%) in the DMARDs group (P = 0.04). Conclusions. Patients with anti-TNF + DMARDs had a greater improvement in FVC% and cardiopulmonary scales at 24 months compared with DMARDs. This preliminary study supports the fact that anti-TNF agents may offer additional benefits compared to DMARDs in patients with AS who have reduced FVC%. PMID:26078986

  11. Violent Reinjury and Mortality Among Youth Seeking Emergency Department Care for Assault-Related Injury A 2-Year Prospective Cohort Study

    PubMed Central

    Cunningham, Rebecca M.; Carter, Patrick M.; Ranney, Megan; Zimmerman, Marc A.; Blow, Fred C.; Booth, Brenda M.; Goldstick, Jason; Walton, Maureen A.

    2015-01-01

    IMPORTANCE Violence is a leading cause of morbidity and mortality among youth, with more than 700 000 emergency department (ED) visits annually for assault-related injuries. The risk for violent reinjury among high-risk, assault-injured youth is poorly understood. OBJECTIVE To compare recidivism for violent injury and mortality outcomes among drug-using, assault-injured youth (AI group) and drug-using, non–assault-injured control participants (non-AI group) presenting to an urban ED for care. DESIGN, SETTING, AND PARTICIPANTS Participants were enrolled in a prospective cohort study from December 2, 2009, through September 30, 2011, at an urban level I ED and followed up for 24 months. We administered validated measures of violence and substance use and mental health diagnostic interviews and reviewed medical records at baseline and at each point of follow-up (6, 12, 18, and 24 months). EXPOSURE Follow-up over 24 months. MAIN OUTCOMES AND MEASURES Use of ED services for assault or mortality measured from medical record abstraction supplemented with self-report. RESULTS We followed 349 AI and 250 non-AI youth for 24 months. Youth in the AI group had almost twice the risk for a violent injury requiring ED care within 2 years compared with the non-AI group (36.7% vs 22.4%; relative risk [RR], 1.65 [95% CI, 1.25-2.14]; P < .001). Two-year mortality was 0.8%. Poisson regression modeling identified female sex (RR, 1.30 [95% CI, 1.02-1.65]), assault-related injury (RR, 1.57 [95% CI, 1.19-2.04), diagnosis of a drug use disorder (RR, 1.29 [95% CI, 1.01-1.65]), and posttraumatic stress disorder (RR, 1.47 [95% CI, 1.09-1.97]) at the index visit as predictive of ED recidivism or death within 24 months. Parametric survival models demonstrated that assault-related injury (P < .001), diagnosis of posttraumatic stress disorder (P = .008), and diagnosis of a drug use disorder (P = .03) significantly shortened the expected waiting time until the first ED return visit for violence

  12. Comparison of olanzapine long-acting injection and oral olanzapine: a 2-year, randomized, open-label study in outpatients with schizophrenia.

    PubMed

    Detke, Holland C; Weiden, Peter J; Llorca, Pierre-Michel; Choukour, Moutaz; Watson, Susan B; Brunner, Elizabeth; Ascher-Svanum, Haya

    2014-08-01

    We compared long-term treatment effectiveness of monthly olanzapine long-acting injection (LAI) with that of oral olanzapine. Outpatients with 2 or more episodes of psychotic worsening in the past 24 months with Positive and Negative Syndrome Scale total score of lower than 70 were randomized to 405 mg/4 weeks of olanzapine LAI (n = 264) or 10 mg/d of oral olanzapine (n = 260) for 2 years of open-label treatment. Dosing thereafter was flexible (150-405 mg/4 weeks of LAI vs 5-20 mg/d of oral). Primary outcome was time to all-cause discontinuation. At baseline, patients were clinically stable (mean Positive and Negative Syndrome Scale total score of 57). Seventeen percent of patients had been psychiatrically hospitalized in the previous 6 months, and 4.6% were rated nonadherent in the month before study entry. The groups did not differ significantly in median time to all-cause discontinuation (645 days for LAI, 678 days for oral; P = 0.61), discontinuation rate (53.8% for LAI, 51.2% for oral; P = 0.60), or relapse rate (20.1% for LAI, 18.5% for oral; P = 0.66). Postbaseline psychiatric hospitalization rate was low for both groups (7.6% for LAI, 9.2% for oral), but mean hospitalization duration was significantly longer for oral patients (1.80 days [20 for those hospitalized] vs 0.43 days [6 for those hospitalized], P = 0.02). There were no clinically significant group differences in adverse events or safety measures. No post-injection delirium/sedation syndrome events occurred. In conclusion, olanzapine LAI and oral olanzapine were similarly effective and well tolerated for up to 2 years of treatment in patients with schizophrenia. Treatment discontinuation for olanzapine LAI was similar to that of oral olanzapine, despite the 3-hour post-injection observation period and other precautionary procedures related to risk of post-injection delirium/sedation syndrome. PMID:24781441

  13. Working memory arrest in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder: results from a 2-year longitudinal study.

    PubMed

    Andersen, Per N; Skogli, Erik W; Hovik, Kjell T; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-05-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically developing children (age 9-16 years) were included at baseline and followed up approximately 25 months later. The children were given a letter/number sequencing task to assess verbal working memory. The performance of children with high-functioning autism on verbal working memory did not improve after 2 years, while improvement was observed in children with attention-deficit/hyperactivity disorder and typically developing children. The results indicate a different developmental trajectory for verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. More research is needed to construct a developmental framework more suitable for children with autism spectrum disorder. PMID:24604922

  14. Violence and Abuse Against Women Who Have Attempted Suicide by Deliberate Self-Poisoning: A 2-Year Follow-Up Study in Iran.

    PubMed

    Hassanian-Moghaddam, Hossein; Zamani, Nasim; Sarjami, Saeedeh

    2016-04-01

    Sources of data about the occurrence of domestic violence are scarce in Iran. The aim of this study was to evaluate the behavioral effects of different types of domestic violence on women who had attempted suicide by deliberate self-poisoning (DSP). A total of 195 women who had attempted suicide by DSP in response to "violence and abuse" were followed up for 2 years. The most common type of violence, as mentioned by the women themselves as the motive of self-poisoning, was physical abuse (92%) followed by verbal abuse (2.1%), multi-abuses (2.1%), emotional abuse (1.6%), and sexual abuse (1.1%). Suicidal ideation and attempt were more common in those who were consulted sometime after they had initially presented to the hospital with DSP or those who had suffered repeated domestic abuse. It was concluded that invention of methods other than the current consultation system is necessary to prevent repeated suicide attempts among abused women in Iran. PMID:25550168

  15. The performance of moss, grass, and 1- and 2-year old spruce needles as bioindicators of contamination: a comparative study at the scale of the Czech Republic.

    PubMed

    Suchara, Ivan; Sucharova, Julie; Hola, Marie; Reimann, Clemens; Boyd, Rognvald; Filzmoser, Peter; Englmaier, Peter

    2011-05-01

    Moss (Pleurozium schreberi), grass (Avenella flexuosa), and 1- and 2-year old spruce (Picea abies) needles were collected over the territory of the Czech Republic at an average sample density of 1 site per 290km(2). The samples were analysed for 39 elements (Ag, Al, As, Ba, Be, Bi, Ca, Cd, Ce, Co, Cr, Cs, Cu, Fe, Ga, Hg, K, La, Li, Mg, Mn, Mo, Na, Nd, Ni, Pb, Pr, Rb, S, Sb, Se, Sn, Sr, Th, Tl, U, V, Y and Zn) using ICP-MS and ICP-AES techniques (the major nutrients Ca, K, Mg and Na were not analysed in moss). Moss showed by far the highest element concentrations for most elements. Exceptions were Ba (spruce), Mn (spruce), Mo (grass), Ni (spruce), Rb (grass) and S (grass). Regional distribution maps and spatial trend analysis were used to study the suitability of the four materials as bioindicators of anthropogenic contamination. The highly industrialised areas in the north-west and the far east of the country and several more local contamination sources were indicated in the distribution maps of one or several sample materials. At the scale of the whole country moss was the best indicator of known contamination sources. However, on a more local scale, it appeared that spruce needles were especially well suited for detection of urban contamination. PMID:21421258

  16. A 2-Year Field Study Shows Little Evidence That the Long-Term Planting of Transgenic Insect-Resistant Cotton Affects the Community Structure of Soil Nematodes

    PubMed Central

    Li, Xiaogang; Liu, Biao

    2013-01-01

    Transgenic insect-resistant cotton has been released into the environment for more than a decade in China to effectively control the cotton bollworm (Helicoverpa armigera) and other Lepidoptera. Because of concerns about undesirable ecological side-effects of transgenic crops, it is important to monitor the potential environmental impact of transgenic insect-resistant cotton after commercial release. Our 2-year study included 1 cotton field where non-transgenic cotton had been planted continuously and 2 other cotton fields where transgenic insect-resistant cotton had been planted for different lengths of time since 1997 and since 2002. In 2 consecutive years (2009 and 2010), we took soil samples from 3 cotton fields at 4 different growth stages (seedling, budding, boll-forming and boll-opening stages), collected soil nematodes from soil with the sugar flotation and centrifugation method and identified the soil nematodes to the genus level. The generic composition, individual densities and diversity indices of the soil nematodes did not differ significantly between the 2 transgenic cotton fields and the non-transgenic cotton field, but significant seasonal variation was found in the individual densities of the principal trophic groups and in the diversity indices of the nematodes in all 3 cotton fields. The study used a comparative perspective to monitor the impact of transgenic insect-resistant cotton grown in typical ‘real world’ conditions. The results of the study suggested that more than 10 years of cultivation of transgenic insect-resistant cotton had no significant effects–adverse or otherwise–on soil nematodes. This study provides a theoretical basis for ongoing environmental impact monitoring of transgenic plants. PMID:23613899

  17. Known occupational carcinogens and their significance.

    PubMed Central

    Ernst, P.; Thériault, G.

    1984-01-01

    Although rates of occupational cancer can be excessive in certain industries, less than 5% of all cancers seem attributable to exposure to carcinogens in the workplace. For example, workers in hard-rock mining and the woodworking industries are at increased risk; cigarette smoking has a synergistic effect. There is conclusive evidence of carcinogenicity for fewer than 20 substances, including asbestos, arsenic, chromium, nickel, cadmium, radon, several aromatic hydrocarbons and certain herbicides. Most of the hundreds of organic compounds known to be mutagenic in in-vitro tests have not been shown to be carcinogenic in epidemiologic studies. Both laboratory and epidemiologic approaches, however, can identify probable causes of cancer and permit the application of effective preventive measures. In addition, it is still possible for the alert individual clinician to make the initial discovery of an occupational hazard. PMID:6367918

  18. Long-term impact of a chef on school lunch consumption: findings from a 2-year pilot study in Boston middle schools.

    PubMed

    Cohen, Juliana F W; Smit, Liesbeth A; Parker, Ellen; Austin, S Bryn; Frazier, A Lindsay; Economos, Christina D; Rimm, Eric B

    2012-06-01

    School cafeterias can play an important role in providing healthy meals. Although schools participating in the National School Lunch Program are required to meet minimum program standards, advocates recommend that innovations be sought to enhance menu dietary quality. This study evaluated the Chef Initiative, a 2-year pilot study in two Boston middle schools, designed to increase the availability and consumption of healthier school foods. Between 2007 and 2009, a professional chef trained cafeteria staff to prepare healthier school lunches (ie, more whole grains, fresh/frozen fruits and vegetables, and less sugar, salt, saturated fats, and trans fats). Meal nutrient compositions were monitored from 2007 to 2009, and a plate waste study conducted in the spring of 2009 compared food selection and consumption patterns among students at Chef Initiative schools, with students receiving standard school lunches at two matched control schools. Paired t tests and descriptive statistics were used to examine differences in menus and mixed-model analysis of variance was used to analyze differences in students' food selection and consumption between Chef Initiative and control schools. Overall, the Chef Initiative schools provided healthier lunches and the percent of foods consumed at Chef Initiative and control schools were similar (61.6% vs 57.3%; P=0.63). Of the areas targeted, there was greater whole-grain selection and vegetable consumption; 51% more students selected whole grains (P=0.02) and students consumed 0.36 more vegetable servings/day (P=0.01) at Chef Initiative schools. The potential of chefs collaborating with cafeteria staff to improve the availability, selection, and consumption of healthier meals is promising. PMID:22504283

  19. The incidence and risk factors for shipping fever in horses transported by air to Hong Kong: Results from a 2-year prospective study.

    PubMed

    Hurley, M J; Riggs, C M; Cogger, N; Rosanowski, S M

    2016-08-01

    A 2 year prospective study was performed between February 2011 and January 2013 to determine the incidence and risk factors for shipping fever (SF) in horses transported by air to Hong Kong (HK). Using a questionnaire, data were collected from professional flying grooms regarding the journey to HK and horses in the shipment. Horses were monitored in quarantine for 2 weeks after arrival in HK, and clinical signs of SF recorded. Poisson and logistic regression models were used to identify risk factors for SF at the horse and shipment levels. The study analysed data from 869 horses on 81 flights arriving from Australia (n = 24), New Zealand (NZ; n = 18), the United Kingdom (UK; n = 33) and the United States of America (USA; n = 6). The incidence risk of SF was 10.8 per 100 horses and the proportion of shipments with at least one horse that developed SF was 49/81 (60%). The study identified that the rate per shipment of SF in shipments of horses originating from NZ, the USA and the UK was 2.40 (95% confidence interval [CI] 1.22-4.71), 2.43 (95% CI 0.66-8.89) and 3.08 (95% CI 1.60-5.93) times the rate of SF compared to Australia. Shipments arriving in HK during March and May were 5.61 (95% CI 1.55-20.31) and 4.51 (95% CI 1.43-14.26) times more likely to contain horses that developed SF compared to shipments arriving in January. The identification of these risk factors and the recognition of at-risk shipments will help focus attention on preventative strategies. PMID:27387724

  20. Emotional Development: 2 Year Olds

    MedlinePlus

    ... Español Text Size Email Print Share Emotional Development: 2 Year Olds Page Content Article Body It’s so ... to follow the ups and downs of a two-year-old. One moment he’s beaming and friendly; ...

  1. Allergic contact sensitizing chemicals as environmental carcinogens.

    PubMed Central

    Albert, R E

    1997-01-01

    Chemicals that were bioassayed by the National Toxicology Program (NTP) and that also produce allergic dermatitis (ACD) in humans were evaluated for their tumorigenic characteristics. The impetus for the study was that most contact sensitizers, i.e., those that produce ACD, and genotoxic carcinogens are chemically similar in that they are electrophilic, thereby producing adducts on macromolecules including protein and DNA. This similarity in chemical behavior suggests that many contact sensitizers might be environmental carcinogens. All of the published NTP bioassays by early 1996 that had both genotoxicity and carcinogenicity studies were included in this analysis. The NTP chemicals had been chosen for bioassay without regard to their ability to produce ACD. Of the 209 chemicals that were bioassayed, there were 36 (17%) that were known to be human contact sensitizers; about half of these were positive on tumor bioassays. The contact sensitizers differed from the NTP sample as a whole by having a proportionately larger number of nongenotoxic chemicals by the Ames Salmonella assay, presumably because more of them were selected on the basis of widespread usage rather than structural resemblance to known carcinogens. Compared to the nongenotoxic chemicals, the genotoxics were stronger carcinogens in that they had a higher incidence of positive tumor bioassays, with twice the number of organs in which tumors were induced. The nongenotoxic chemicals had a preference for tumor induction in parenchymal tissues in contrast to epithelial tissues. The contact sensitizers showed essentially the same characteristics as the whole NTP sample when stratified according to genotoxicity. Judging by the chemicals that were chosen primarily for their widespread use rather than for their structural resemblance to carcinogens, the addition of a test for contact sensitization to the Ames test as a screening tool would increase the tumorigenic detection efficiency by about 40% because of

  2. A Multicenter, Single-Blind Randomized, Controlled Study of a Volumizing Hyaluronic Acid Filler for Midface Volume Deficit: Patient-Reported Outcomes at 2 Years

    PubMed Central

    Few, Julius; Cox, Sue Ellen; Paradkar-Mitragotri, Deepali; Murphy, Diane K.

    2015-01-01

    Background Juvéderm Voluma XC is a volumizing hyaluronic acid filler used for correction of age-related midface volume deficit (MVD). Objectives The effectiveness of Juvéderm Voluma XC was examined from the patient perspective. Methods Patients with moderate to severe age-related MVD (N = 235) received Juvéderm Voluma XC. At quarterly follow-up visits for 2 years, patients rated treatment outcomes on the Global Aesthetic Improvement Scale (GAIS), overall satisfaction with facial appearance, satisfaction with midfacial regions, achievement of treatment goal, Look and Feel of the Midface (LAFM), and Self-Perception of Age (SPA). Patients recorded treatment-site responses in 30-day diaries. Results At 6 months and 2 years after treatment, 92.8% and 79.0% of patients, respectively, rated their cheek volume as improved/much improved on the GAIS. Improvement in satisfaction with facial appearance was noted by 89.8% of patients at 6 months and 75.8% at 2 years. Increased satisfaction with outer and lower cheek areas and cheek-bone projection and clinically significant improvements in LAFM were noted through month 24. Treatment goals were achieved by 67.8% of patients at 6 months and 49.0% at 2 years. Patients reported looking, on average, 5 years younger at 6 months and 3 years younger at 2 years. The most common treatment site responses were tenderness, swelling, firmness, and lumps/bumps; most were mild to moderate in severity and lasted ≤2 weeks. Conclusions Juvéderm Voluma XC for age-related MVD is effective and well-tolerated from the patient perspective, with results lasting up to 2 years. Level of Evidence 4 Therapeutic PMID:25964628

  3. Revision Total Hip Arthroplasty Using Tantalum Augment in Patients with Paprosky III or IV Acetabular Bone Defects: A Minimum 2-year Follow Up Study

    PubMed Central

    Jeong, Min; Kim, Hyung-Joo; Lim, Seung-Jae; Moon, Young-Wan

    2016-01-01

    Purpose The purpose of this study is to report the short-term outcomes of revision total hip arthroplasty (THA) using tantalum augments in patients with severe acetabular bone defects. Materials and Methods We retrospectively analyzed 15 revision THAs performed in 15 patients using tantalum augments between June 2010 and December 2013. Acetabular bone defects were Paprosky type IIIA in 7 hips, type IIIB in 7, and type IV in 1. The causes of revision surgery were aseptic loosening in 12 hips and deep infection in 3. Revisions were first in 1 hip, second in 3, and third in 11. Six patients were male and 9 female with a mean age of 59 years (range, 48-75 years). Mean follow-up was 29 months (range, 24-48 months). Results Mean Harris hip score was improved from 34 points (range, 12-54 points) preoperatively to 84 points (range, 38-90 points) at final follow-up. On the final follow-up radiographs, there were 12 hips (80.0%) with stable fixation of the acetabular cup, 2 (13.3%) with secondary stability after mild acetabular protrusion, and 1 (6.7%) with radiolucency around the acetabular cup without mechanical symptoms. Complications included one patient with acute hematogenous infection managed by surgical debridement and long-term antibiotic therapy. There were no cases with nerve palsy or dislocation during the follow-up period. Conclusion The present study showed satisfactory clinical and radiographic outcomes of revision THA using tantalum augments due to severe acetabular bone defects of Paprosky type III or IV at a minimum follow-up of 2 years. PMID:27536651

  4. Comparison of one-level microendoscopy laminoforaminotomy and cervical arthroplasty in cervical spondylotic radiculopathy: a minimum 2-year follow-up study

    PubMed Central

    2013-01-01

    Background This study aims to compare the perioperative parameters and clinical results between microendoscopy laminoforaminotomy (MELF) and cervical arthroplasty (CA) in the treatment of one-level cervical spondylotic radiculopathy in a retrospective study. Methods From 2003 to 2007, a total of 97 patients with one-level cervical spondylotic radiculopathy were treated. Forty-five patients underwent CA. Fifty-two patients underwent MELF. Patient demographics and operative data were collected with a minimum 2-year follow-up. Perioperative parameters were compared. Clinical assessment in terms of neck disability index (NDI), short form (SF)-36, and visual analogue scale (VAS) of arm pain and neck pain was performed prior to surgery and at 1.5, 3, 6, 12, and 24 months after surgery. Results Fluoroscopy time (CA, 60.3 s; MELF, 12.1 s; P < 0.01) and surgical time (CA, 95.1 min; MELF, 24.0 min; P < 0.01) were significantly longer in the CA cases. Shorter hospitalized days (CA, 1.1 days; MELF, 0.13 days; P < 0.01) and less estimated blood loss (EBL; CA, 75.8 ml; MELF, 31.9 ml; P < 0.01) were observed in the MELF group. Both CA and MELF groups showed significant improvement in NDI, VAS of neck pain and arm pain, and SF-36 (P < 0.05 for each) at 1.5, 3, 6, 12, and 24 months after surgery, but there was no significant difference between them (P > 0.05). Conclusions As alternatives of anterior cervical decompression and fusion (ACDF), both CA and MELF can produce satisfactory clinical outcomes. MELF has the additional benefits of less blood loss, less surgical time, less X-ray time, and shorter hospital stay. PMID:24341633

  5. Imaging of the dopamine transporter predicts pattern of disease progression and response to levodopa in patients with schizophrenia and parkinsonism: a 2-year follow-up multicenter study.

    PubMed

    Tinazzi, Michele; Morgante, Francesca; Matinella, Angela; Bovi, Tommaso; Cannas, Antonino; Solla, Paolo; Marrosu, Francesco; Nicoletti, Alessandra; Zappia, Mario; Luca, Antonina; Di Stefano, Angela; Morgante, Letterio; Pacchetti, Claudio; Minafra, Brigida; Sciarretta, Massimo; Dallocchio, Carlo; Rossi, Simone; Ulivelli, Monica; Ceravolo, Roberto; Frosini, Daniela; Cipriani, Andrea; Barbui, Corrado

    2014-02-01

    Similarly to subjects with degenerative parkinsonism, (123)I-FP-CIT SPECT has been reported either normal or abnormal in patients with drug-induced parkinsonism (DIP), challenging the notion that parkinsonism might be entirely due to post-synaptic D2-receptors blockade by antipsychotic drugs. In a previous multicenter cross-sectional study conducted on a large sample of patients with schizophrenia, we identified 97 patients who developed parkinsonism with a similar bi-modal distribution of DAT-SPECT. In this longitudinal study, we reported clinical and imaging features associated with progression of motor disability over 2-year follow-up in 60 out of those 97 patients with schizophrenia and parkinsonism who underwent (123)I-FP-CIT SPECT at baseline evaluation (normal SPECT=33; abnormal SPECT=27). As second end-point, chronic response to levodopa over a 3-month period was tested in a subgroup of subjects. Motor Unified Parkinson's Disease Rating Scale (UPDRS) at follow-up significantly increased in patients with abnormal SPECT. Specifically, a 6-point worsening was demonstrated in 18.5% of the subjects with abnormal SPECT and in none of the subjects with normal SPECT. Levodopa treatment improved motor UPDRS only in the group with abnormal SPECT. After adjustment for possible confounders, linear regression analysis demonstrated that abnormal SPECT findings at baseline were the only predictor of motor disability progression and of better outcome of levodopa treatment. Our results support the notion that a degenerative disease might underlie parkinsonism in a minority of schizophrenic patients chronically exposed to antipsychotics. Functional imaging of the dopamine transporter can be helpful to select this patient sub-group that might benefit from levodopa therapy. PMID:24369987

  6. Increased Regulatory T-Cell Percentage Contributes to Poor CD4+ Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy

    PubMed Central

    Saison, Julien; Maucort Boulch, Delphine; Chidiac, Christian; Demaret, Julie; Malcus, Christophe; Cotte, Laurent; Poitevin-Later, Francoise; Miailhes, Patrick; Venet, Fabienne; Trabaud, Mary Anne; Monneret, Guillaume; Ferry, Tristan

    2015-01-01

    Background. The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods. A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count <500 cells/mm3. Regulatory T cells were identified as CD4+CD25highCD127low cells among CD4+ lymphocytes. Effect of Treg percentage at inclusion on CD4 evolution overtime was analyzed using a mixed-effect Poisson regression for count data. Results. Fifty-eight patients were included (median CD4 = 293/mm3, median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm3 increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions. Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir. PMID:26110165

  7. Quantitation of pyridyloxobutyl-DNA adducts in tissues of rats treated chronically with (R)- or (S)-N'-nitrosonornicotine (NNN) in a carcinogenicity study.

    PubMed

    Zhao, Lijiao; Balbo, Silvia; Wang, Mingyao; Upadhyaya, Pramod; Khariwala, Samir S; Villalta, Peter W; Hecht, Stephen S

    2013-10-21

    We quantified DNA adducts resulting from 2'-hydroxylation of enantiomers of the tobacco-specific nitrosamine N'-nitrosonornicotine (NNN) in tissues of male F-344 rats after 10, 30, 50, and 70 weeks of treatment with 14 ppm in the drinking water. These rats were in subgroups of a carcinogenicity study in which (S)-NNN was highly tumorigenic in the oral cavity and esophagus, while (R)-NNN was relatively weakly active. DNA adducts were quantified by liquid chromatography-electrospray ionization-tandem mass spectrometry in six tissues: oral mucosa, esophageal mucosa, nasal respiratory mucosa, nasal olfactory mucosa, liver, and lung. O²-[4-(3-Pyridyl)-4-oxobut-1-yl]thymidine (O²-POB-dThd, 7) and 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2'-deoxyguanosine (7-POB-dGuo, 8), the latter as 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine (7-POB-Gua, 11), were detected at each time point in each tissue. In the target tissues for carcinogenicity, oral mucosa and esophageal mucosa, levels of 7-POB-Gua (11) and O²-POB-dThd (7) were similar, or 11 predominated, while in all other tissues at all time points for both enantiomers, 7 was clearly present in greater amounts than 11. Total measured DNA adduct levels in esophageal mucosa and oral mucosa were higher in rats treated with (S)-NNN than (R)-NNN. The highest adduct levels were found in the nasal respiratory mucosa. DNA adducts generally persisted in all tissues without any sign of substantial decreases throughout the 70 week time course. The results of this study suggest that inefficient repair of 7-POB-dGuo (8) in the rat oral cavity and esophagus may be important in carcinogenesis by NNN and support the development of these DNA adducts as potential biomarkers of NNN metabolic activation in people who use tobacco products. PMID:24001146

  8. The temporal variability of the profile of carcinogenic polycyclic aromatic hydrocarbons in urban air: a study in a medium traffic area in Rome, 1993-1998

    NASA Astrophysics Data System (ADS)

    Menichini, E.; Monfredini, F.; Merli, F.

    The constancy, both temporal and spatial, of the profile of polycyclic aromatic hydrocarbons (PAHs) relative to benzo[a]pyrene (BaP) is a prerequisite to using the BaP-indicator approach in the carcinogenic risk assessment for PAHs. The principal aim of this study was to provide a contribution to validate this approach, by studying the variability of the profile at a typical urban site through a multi-year data set and by comparing the profiles available for different cities. Seven carcinogenic PAHs (benz[a]anthracene, benzo[b+j+k]fluoranthenes, BaP, indeno[1,2,3-cd]pyrene, dibenz[a,h]anthracene) were determined in PM 10 24-h samples collected every third day at a road site; moreover, benzo[e]pyrene was determined as a reference PAH due to its stability. The profile was found stable from year to year. Besides, it was similar to those recently found in other European cities (observed differences within a factor of four) and to those elaborated from earlier (1970s-1980s) investigations. The substantial similarity of profiles, both temporal (on an annual basis) and spatial, supports the validity of the BaP-indicator approach. Large PAH-to-PAH differences were, however, found in the seasonal pattern of profile: they were explained by the different atmospheric degradability of PAHs, whose effect is enhanced under the meteoclimatic conditions typical of the European Mediterranean countries. PAH annual means showed a slight declining trend since 1994. In the last sampling year, mean concentration of BaP was 1.2 ng m -3. Within-year differences among monthly averaged PAH concentrations were observed, as large as up to 44-fold for BaP, underlining the need for whole-year monitoring.

  9. Dasatinib in Imatinib-Resistant or Imatinib-Intolerant Chronic Myeloid Leukemia in Blast Phase After 2 Years of Follow-Up in a Phase 3 Study

    PubMed Central

    Saglio, Giuseppe; Hochhaus, Andreas; Goh, Yeow Tee; Masszi, Tamas; Pasquini, Ricardo; Maloisel, Frederic; Erben, Philipp; Cortes, Jorge; Paquette, Ronald; Bradley-Garelik, M. Brigid; Zhu, Chao; Dombret, Herve

    2016-01-01

    BACKGROUND In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported. METHODS Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily. RESULTS In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen. CONCLUSIONS The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML. PMID:20564086

  10. Scaling up family medicine training in Gezira, Sudan – a 2-year in-service master programme using modern information and communication technology: a survey study

    PubMed Central

    2014-01-01

    Background In 2010 the Gezira Family Medicine Project (GFMP) was initiated in Gezira state, Sudan, designed as an in-service training model. The project is a collaboration project between the University of Gezira, which aims to provide a 2-year master’s programme in family medicine for practicing doctors, and the Ministry of Health, which facilitates service provision and funds the training programme. This paper presents the programme, the teaching environment, and the first batch of candidates enrolled. Methods In this study a self-administered questionnaire was used to collect baseline data at the start of the project from doctors who joined the programme. A checklist was also used to assess the health centres where they work. A total of 188 out of 207 doctors responded (91%), while data were gathered from all 158 health centres (100%) staffed by the programme candidates. Results The Gezira model of in-service family medicine training has succeeded in recruiting 207 candidates in its first batch, providing health services in 158 centres, of which 84 had never been served by a doctor before. The curriculum is community oriented. The mean age of doctors was 32.5 years, 57% were males, and 32% were graduates from the University of Gezira. Respondents stated high confidence in practicing some skills such as asthma management and post-abortion uterine evacuation. They were least confident in other skills such as managing depression or inserting an intrauterine device. The majority of health centres was poorly equipped for management of noncommunicable diseases, as only 10% had an electrocardiography machine (ECG), 5% had spirometer, and 1% had a defibrillator. Conclusions The Gezira model has responded to local health system needs. Use of modern information and communication technology is used to facilitate both health service provision and training. The GFMP represents an example of a large-volume scaling-up programme of family medicine in Africa. PMID:24443978

  11. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  12. PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC

    EPA Science Inventory

    PROPOSED CARCINOGENIC MECHANISMS FOR ARSENIC.

    Arsenic is a human carcinogen in skin, lung, liver, urinary bladder and kidney. In contrast,
    there is no accepted experimental animal model of inorganic arsenic carcinogenesis.
    Proposed mechanisms/modes of action for a...

  13. Carcinogenicity study with technical-grade dichlorodiphenyltrichloroethane and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene in hamsters.

    PubMed

    Rossi, L; Barbieri, O; Sanguineti, M; Cabral, J R; Bruzzi, P; Santi, L

    1983-02-01

    Studies conducted by others have revealed that 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a proximal metabolite of dichlorodiphenyltrichloroethane (DDT), is a strong hepatocellular carcinogen in mice. Since hamsters appear to be resistant to tumor induction by DDT, we wanted to investigate whether DDE has any neoplastic effect in this species. DDE (99% pure) was mixed into the diet at doses of 500 or 1000 ppm and given to groups of male and female Syrian golden hamsters for life. Another group of animals received a diet containing 1000 ppm technical-grade DDT, and a further group served as control. Groups contained a minimum of 40 hamsters per sex. The tested compounds had no effect on the incidence of tumors at all sites, compared to controls. A specific finding in animals exposed to DDE was the appearance of hepatocellular tumors late in life. They were classified as neoplastic nodules, and the incidence was 15% in females and 47% in males of the 500-ppm DDE dose groups and 21% in females and 33% in males of the 1000-ppm DDE dose groups. None of the untreated or DDT-treated animals had these tumors. Eight animals treated with 1000 ppm DDE and four of those treated with DDT had hyperplastic foci of the liver. In addition, adrenocortical adenomas, spontaneous to Syrian golden hamsters, were more frequent in DDE- and DDT-treated animals than in control animals. These results showing that DDE, but not its parental compound, induces liver cell tumors in hamsters emphasize the importance of this metabolite as a proximal carcinogen of DDT. PMID:6848191

  14. The Limits of Two-Year Bioassay Exposure Regimens for Identifying Chemical Carcinogens

    PubMed Central

    Huff, James; Jacobson, Michael F.; Davis, Devra Lee

    2008-01-01

    Background Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. Objectives In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Discussion Studies of three chemicals of different structures and uses—aspartame, cadmium, and toluene—suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Conclusions Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives. PMID:19057693

  15. CARCINOGENIC EFFECTS OF BENZENE: AN UPDATE (FINAL)

    EPA Science Inventory

    The major issue addressed in this document involves the nature and magnitude of the risk of cancer to humans exposed to low levels of benzene. Occupational studies continue to provide the bulk of evidence of benzenes carcinogenicity. Workers are exposed at much higher levels than...

  16. CARCINOGEN RISK ASSESSMENT OF CHROMIUM COMPOUNDS

    EPA Science Inventory

    Hexavalent chromium has been identified as a human carcinogen. Evidence to support this contention derives from epidemiologic, animal, and genotoxicity studies. Although workers exposed to both trivalent and hexavalent chromium have been shown to be at an excess risk of respirato...

  17. Carcinogen Control in the Chemical Laboratory.

    ERIC Educational Resources Information Center

    Johnson, James S.

    1981-01-01

    Presents general and specific guidelines for handling carcinogens. Additional topics include: definition of potential occupational carcinogens; classification of carcinogens; inventory requirements; signs and labels for materials and laboratories; decontamination and disposal procedures; medical surveillance for employees working with controlled…

  18. Factors Predicting Patient Dissatisfaction 2 Years After Discectomy for Lumbar Disc Herniation in a Chinese Older Cohort: A Prospective Study of 843 Cases at a Single Institution.

    PubMed

    Wang, Hui; Zhang, Di; Ma, Lei; Shen, Yong; Ding, Wenyuan

    2015-10-01

    We aim to identify factors predicting patient dissatisfaction 2 years after discectomy for lumbar disc herniation (LDH) in a Chinese older cohort. Preoperative and 2-year follow-up data for 843 patients were analyzed. After 2 years of discectomy, the patients rated their satisfaction by Patient Satisfaction Index (PSI), with response of 1 or 2 defining satisfaction and a PSI response of 3 or 4 defining dissatisfaction. Associations between perioperative variables and satisfaction with the results of surgery were examined in univariate and multivariate analysis. Six hundred fifty-seven patients had a PSI of 1 or 2 and were enrolled as satisfied group, 186 patients had a PSI of 3 or 4 and were enrolled as dissatisfied group. At baseline, no significant differences were found between the 2 groups in age, occupation, Oswestry Disability Index (ODI), Visual Analog Scale (VAS)-leg, and VAS-back. Compared to satisfied group, dissatisfied group had a significantly higher BMI and a higher incidence of depression. Two years after discectomy, no significant differences were found between the 2 groups in decrease of ODI, decrease of VAS-back, decrease of VAS-leg, surgery complications. Compared to satisfied group, dissatisfied group experienced higher incidence of symptom recurrence and depression. Logistic regression analysis showed that obesity, pre- and postoperative depression, symptom recurrence were independently associated with patient dissatisfaction 2 years after discectomy.I n conclusion, more than 70% patients expressed satisfaction with discectomy for LDH. Two factors could predict patient dissatisfaction and be assessed before surgery: obesity and preoperative depression. Symptom recurrence and postoperative depression are also associated with diminished patient satisfaction. PMID:26448005

  19. Immunologic methods for monitoring carcinogen exposure

    NASA Astrophysics Data System (ADS)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  20. Detection of genotoxic and non-genotoxic carcinogens in Xpc{sup −/−}p53{sup +/−} mice

    SciTech Connect

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-15

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  1. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF 1,2-DIMETHYL-HYDRAZINE

    EPA Science Inventory

    1,2-Dimethylhydrazine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is sufficient," and the evidence from human studies ...

  2. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF 1,1-DIMETHYL-HYDRAZINE

    EPA Science Inventory

    1,1-Dimethylhydrazine is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is sufficient,n and the evidence from human studies ...

  3. Markers of exposure to carcinogens.

    PubMed Central

    Wogan, G N

    1989-01-01

    Methods have been developed for the detection of exposure to carcinogens and other DNA damaging agents in experimental animals and man through the detection of carcinogens or their metabolic derivatives in body fluids, or through adducts bound covalently to DNA or hemoglobin. The successful use of urinary markers of genotoxic exposures has been reported with respect to nitrosoproline as an indicator of exposure to N-nitroso compounds. The same approach has been used to detect AFB1 and AFB1-N7-Gua as markers of exposure to aflatoxin B1; of 3-methyladenine produced as a result of exposure to methylating agents; and thymine glycol as an indicator of exposure to agents causing oxidative damage to DNA. Detection of adducts formed between genotoxic agents and hemoglobin has been reported in studies of populations occupationally exposed to ethylene oxide, in which 3-hydroxyhistidine and 3-hydroxyvaline have been measured, and in smokers, whose hemoglobin has been found to contain levels of 4-aminobiphenyl and 3-hydroxyvaline that were correlated with the frequency of cigarette smoking. Detection of DNA adducts of genotoxic agents in the cells and tissues of exposed individuals has also been accomplished through the use of several types of analytical methods. Immunoassays and physicochemical methods have been applied to detect adducts formed through the major intermediate in the activation of benzo(a)pyrene, the 7,8-diol-9,10-epoxide (BPDE). This adduct has been found in the DNA of peripheral leukocytes of workers in foundries, aluminum manufacturing plants, roofers, and coke oven plants, and also in cigarette smokers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2667991

  4. Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p-phenylenediamine and other aromatic amines.

    PubMed

    Burnett, C M; Goldenthal, E I

    1988-05-01

    Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl-p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were

  5. Carcinogens formed when Meat is Cooked

    SciTech Connect

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

  6. N,N-dimethyl-p-toluidine, a component in dental materials, causes hematologic toxic and carcinogenic responses in rodent model systems.

    PubMed

    Dunnick, June K; Brix, A; Sanders, J M; Travlos, G S

    2014-01-01

    Because of the potential for exposure to N,N-dimethyl-p-toluidine (DMPT) in medical devices and the lack of toxicity and carcinogenicity information available in the literature, the National Toxicology Program conducted toxicity and carcinogenicity studies of DMPT in male and female F344/N rats and B6C3F1/N mice. In these studies, a treatment-related macrocytic regenerative anemia characterized by increased levels of methemoglobin and Heinz body formation developed within a few weeks of DMPT exposure in rats and mice. DMPT induced nasal cavity, splenic, and liver toxicity in rats and mice at 3 months and 2 years. DMPT carcinogenic effects were seen in the liver of male and female rats and mice, the nasal cavity of male and female rats, and the lung and forestomach of female mice. In rodents, DMPT is distributed to many of the sites where toxic and carcinogenic effects occurred. DMPT-induced oxidative damage at these target sites may be one mechanism for the treatment-related lesions. Methemoglobinemia, as seen in these DMPT studies, is caused by oxidation of the heme moiety, and this end point served as an early alert for other target organ toxicities and carcinogenic responses that followed with longer term exposure. PMID:23867143

  7. New Walking and Cycling Routes and Increased Physical Activity: One- and 2-Year Findings From the UK iConnect Study

    PubMed Central

    Goodman, Anna; Sahlqvist, Shannon; Ogilvie, David

    2014-01-01

    Objectives. We evaluated the effects of providing new high-quality, traffic-free routes for walking and cycling on overall levels of walking, cycling, and physical activity. Methods. 1796 adult residents in 3 UK municipalities completed postal questionnaires at baseline (2010) and 1-year follow-up (2011), after the construction of the new infrastructure. 1465 adults completed questionnaires at baseline and 2-year follow-up (2012). Transport network distance from home to infrastructure defined intervention exposure and provided a basis for controlled comparisons. Results. Living nearer the infrastructure did not predict changes in activity levels at 1-year follow-up but did predict increases in activity at 2 years relative to those living farther away (15.3 additional minutes/week walking and cycling per km nearer; 12.5 additional minutes/week of total physical activity). The effects were larger among participants with no car. Conclusions. These new local routes may mainly have displaced walking or cycling trips in the short term but generated new trips in the longer term, particularly among those unable to access more distant destinations by car. These findings support the potential for walking and cycling infrastructure to promote physical activity. PMID:25033133

  8. A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study

    PubMed Central

    Beatty, Stephen; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; Si Bouazza, Abdelkader; Pilz, Stefan

    2014-01-01

    Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%–1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, –1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated. PMID:24868458

  9. Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies.

    PubMed

    Isobe, Kaori; Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2016-07-01

    The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID:27559247

  10. Historical control background incidence of spontaneous thyroid and parathyroid glands lesions of rats and CD-1 mice used in 104-week carcinogenicity studies

    PubMed Central

    Isobe, Kaori; Mukaratirwa, Sydney; Petterino, Claudio; Bradley, Alys

    2016-01-01

    The incidence and range of spontaneous thyroid and parathyroid glands findings were determined in control Han-Wistar and Sprague-Dawley rats, and CD-1 mice from 104-week carcinogenicity studies carried out between 1998 and 2010 at Charles River Edinburgh. In both strains of rats and in CD-1 mice, non-proliferative lesions of the thyroid or parathyroid glands were generally uncommon apart from some findings in CD-1 mice such as ultimobranchial duct/cyst (5.72%), follicular distension/dilatation (3.84%), and cystic follicles (3.53%). In Han-Wistar rats, thyroid proliferative lesions were slightly more frequent in males than in females, but in Sprague-Dawley rats, they were of similar incidence in both sexes. The most common findings overall in Han-Wistar and Sprague-Dawley rats were C-cell hyperplasia (48.11% and 36.56%, respectively) and adenoma (10.87% and 9.52%, respectively), follicular cell hyperplasia (4.21% and 0.91%, respectively) and adenoma (4.32% and 1.36%, respectively). Secondary neoplastic lesions either in thyroid or parathyroid gland were poorly represented. PMID:27559247

  11. Application of the U.S. EPA mode of action Framework for purposes of guiding future research: a case study involving the oral carcinogenicity of hexavalent chromium.

    PubMed

    Thompson, Chad M; Haws, Laurie C; Harris, Mark A; Gatto, Nicole M; Proctor, Deborah M

    2011-01-01

    Mode of action (MOA) analysis provides a systematic description of key events leading to adverse health effects in animal bioassays for the purpose of informing human health risk assessment. Uncertainties and data gaps identified in the MOA analysis may also be used to guide future research to improve understanding of the MOAs underlying a specific toxic response and foster development of toxicokinetic and toxicodynamic models. An MOA analysis, consistent with approaches outlined in the MOA Framework as described in the Guidelines for Carcinogen Risk Assessment, was conducted to evaluate small intestinal tumors observed in mice chronically exposed to relatively high concentrations of hexavalent chromium (Cr(VI)) in drinking water. Based on review of the literature, key events in the MOA are hypothesized to include saturation of the reductive capacity of the upper gastrointestinal tract, absorption of Cr(VI) into the intestinal epithelium, oxidative stress and inflammation, cell proliferation, direct and/or indirect DNA modification, and mutagenesis. Although available data generally support the plausibility of these key events, several unresolved questions and data gaps were identified, highlighting the need for obtaining critical toxicokinetic and toxicodynamic data in the target tissue and in the low-dose range. Experimental assays that can address these data gaps are discussed along with strategies for comparisons between responsive and nonresponsive tissues and species. This analysis provides a practical application of MOA Framework guidance and is instructive for the design of studies to improve upon the information available for quantitative risk assessment. PMID:20947717

  12. Cadmium Alters the Biotransformation of Carcinogenic Aromatic Amines by Arylamine N-Acetyltransferase Xenobiotic-Metabolizing Enzymes: Molecular, Cellular, and in Vivo Studies

    PubMed Central

    Ragunathan, Nilusha; Dairou, Julien; Sanfins, Elodie; Busi, Florent; Noll, Christophe; Janel, Nathalie; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

    2010-01-01

    Background Cadmium (Cd) is a carcinogenic heavy metal of environmental concern. Exposure to both Cd and carcinogenic organic compounds, such as polycyclic aromatic hydrocarbons or aromatic amines (AAs), is a common environmental problem. Human arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play a key role in the biotransformation of AA carcinogens. Changes in NAT activity have long been associated with variations in susceptibility to different cancers in relation with exposure to certain AAs. Objective We explored the possible interactions between Cd and the NAT-dependent biotransformation of carcinogenic AAs. Methods We exposed purified enzymes, lung epithelial cells, and mouse models to Cd and subsequently analyzed NAT-dependent metabolism of AAs. Results We found that Cd, at biologically relevant concentrations, impairs the NAT-dependent acetylation of carcinogenic AAs such as 2-aminofluorene (2-AF) in lung epithelial cells. NAT activity was strongly impaired in the tissues of mice exposed to Cd. Accordingly, mice exposed to Cd and 2-AF displayed altered in vivo toxicokinetics with a significant decrease (~ 50%) in acetylated 2-AF in plasma. We found that human NAT1 was rapidly and irreversibly inhibited by Cd [median inhibitory concentration (IC50) ≈ 55 nM; rate inhibition constant (kinact) = 5 × 104 M−1 · sec−1], with results of acetyl coenzyme A (acetyl-CoA) protection assays indicating that Cd-mediated inhibition was due to the reaction of metal with the active-site cysteine residue of the enzyme. We found similar results for human NAT2, although this isoform was less sensitive to inactivation (IC50 ≈ 1 μM; kinact = 1 × 104 M−1 · sec−1). Conclusions Our data suggest that Cd can alter the metabolism of carcinogenic AAs through the impairment of the NAT-dependent pathway, which may have important toxicological consequences. PMID:20810355

  13. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  14. State of the science on the carcinogenicity of gasoline with particular reference to cohort mortality study results

    SciTech Connect

    Infante, P.F.

    1993-12-01

    As a result of the content of benzene in various streams of refinery products, including gasoline, it is not surprising that over the years studies and case reports have linked gasoline exposure to lymphopoietic cancers (LPC), particularly leukemia and multiple myeloma (MM). Of three recently conducted studies of gasoline-exposed workers, one shows strong associations with leukemia and MM, a second suggests some association with leukemia and did not analyze data for MM, and the third study is not possible to evaluate because of a major problem with study design. Other diseases of particular interest in relation to gasoline exposure are kidney cancer, malignant melanoma, and heart disease. One study suggests an association with kidney cancer, but the second study did not. There appears to be no association between employment in refineries or gasoline exposure and heart disease. However, evaluation of risk of kidney cancer and heart disease is somewhat difficult because investigators did not control for cigarette smoking, even though it is related to these diseases. This is of particular concern when studying gasoline-exposed workers, who because of the explosive nature of gasoline probably smoke less than the general population used for comparison of mortality. Some studies of refinery workers and gasoline-exposed workers in particular show an excess risk of death from malignant melanoma. Whether this latter association is the result of benzene/gasoline exposure, sunlight exposure, or a combination of the two cannot be determined with the data currently available. The National Toxicology Program benzene cancer bioassay and the Dow Chemical Company epidemiologic study argue in favor of a benzene etiology; the fact that the workers spend a great amount of time outdoors argues in favor of a sunlight etiology. Finally, the American Petroleum Institute is challenged to apply warning labels and filling instructions to gasoline pumps and containers. 32 refs.

  15. Effects of sediment dredging on nitrogen cycling in Lake Taihu, China: Insight from mass balance based on a 2-year field study.

    PubMed

    Yu, Juhua; Fan, Chengxin; Zhong, Jicheng; Zhang, Lu; Zhang, Lei; Wang, Changhui; Yao, Xiaolong

    2016-02-01

    Sediment dredging can permanently remove pollutants from an aquatic ecosystem, which is considered an effective approach to aquatic ecosystem restoration. In this work, a 2-year field simulation test was carried out to investigate the effect of dredging on nitrogen cycling across the sediment-water interface (SWI) in Lake Taihu, China. The results showed that simulated dredging applied to an area rich in total organic carbon (TOC) and total nitrogen (TN) slightly reduced the NH4(+)-N release from sediments while temporarily enhanced the NH4(+)-N release in an area with lower TOC and/or TN (in the first 180 days), although the application had a limited effect on the fluxes of NO2(-)-N and NO3(-)-N in both areas. Further analysis indicated that dredging induced decreases in nitrification, denitrification, and anaerobic ammonium oxidation (anammox) in sediments, notably by 76.9, 49.0, and 89.9%, respectively, in the TOC and/or TN-rich area. Therefore, dredging slowed down nitrogen cycling rates in sediments but did not increase N loading to overlying water. The main reason for the above phenomenon could be attributed to the removal of the surface sediments enriched with more TOC and/or TN (compared with the bottom sediments). Overall, to minimize internal N pollution, dredging may be more applicable to nutrient-rich sediments. PMID:26499196

  16. Overall false positive rates in tests for linear trend in tumor incidence in animal carcinogenicity studies of new drugs.

    PubMed

    Lin, K K; Rahman, M A

    1998-03-01

    Based on results of simulation and empirical studies conducted within the Divisions of Biometrics, Center for Drug Evaluation and Research, Food and Drug Administration, and in collaboration with the National Toxicology Program, the Center has recently changed the significance levels for testing positive linear trend in incidence rate for common and rare tumors, respectively, from 0.01 and 0.05 to 0.005 and 0.025. The overall false positive rate resulting from the use of this new rule in the tests for linear trend in a two-species-two-sex study is about 10%, the rate that is judged as the most appropriate in a regulatory setting by the Center. This paper describes two of the studies. PMID:9547425

  17. Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study

    PubMed Central

    2010-01-01

    Background The clinical relevance of observations of serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor -κB ligand (RANKL) in juvenile idiopathic arthritis (JIA) is not clear. To elucidate the potential role of OPG and RANKL in JIA we determined serum levels of OPG and RANKL in patients with early JIA compared to healthy children, and prospectively explored changes in relation to radiographic score, bone and lean mass, severity of the disease, and treatment. Methods Ninety children with early oligoarticular or polyarticular JIA (ages 6-18 years; mean disease duration 19.4 months) and 90 healthy children individually matched for age, sex, race, and county of residence, were examined at baseline and 2-year follow-up. OPG and RANKL were quantified by enzyme-immunoassay. Data were analyzed with the use of t-tests, ANOVA, and multiple regression analyses. Results Serum OPG was significantly lower in patients than controls at baseline, and there was a trend towards higher RANKL and a lower OPG/RANKL ratio. Patients with polyarthritis had significantly higher increments in RANKL from baseline to follow-up, compared to patients with oligoarthritis. RANKL was a significant negative predictor for increments in total body lean mass. Patients who were receiving corticosteroids (CS) or disease-modifying antirheumatic drugs (DMARDs) at follow-up had higher OPG/RANKL ratio compared with patients who did not receive this medication. Conclusions The data supports that levels of OPG are lower in patients with JIA compared to healthy children, and higher levels of RANKL is associated with more serious disease. RANKL was a significant negative predictor of lean mass in patients with JIA. The OPG/RANKL ratio was higher in patients on DMARDs or CS treatment. PMID:21134287

  18. Statistical analysis of results of carcinogenicity studies of synthetic vitreous fibres at Research and Consulting Company, Geneva.

    PubMed

    Rossiter, C E; Chase, J R

    1995-10-01

    Five inhalation studies of synthetic vitreous fibres have recently investigated experimental tumorigenic responses to four different refractory ceramic fibres (RCF), two fibre glasses, one stone (rock) wool and one slag wool. Except for one RCF, the source materials were typical commercial products. Three studies included positive control groups exposed to chrysotile or crocidolite asbestos. The studies were conducted using state-of-the-art technologies for fibre size separation, fibre lofting and nose-only inhalation exposure. The target average fibre size was 20 microns long by 1 micron diameter. Hamsters exposed to a kaolin RCF yielded a mesothelioma rate of 38%, but no lung cancers. There were no tumours among the chrysotile-exposed hamsters. At the highest dose of 30 mg m-3 in rat studies, the commercial RCF all produced significant numbers of lung tumours, and some mesotheliomas. The fourth RCF, which had been heat-treated to simulate an after-service fibre, did not produce a significant excess of lung cancers, but did produce one mesothelioma. A rat multi-dose experiment with three lower doses of the kaolin RCF yielded one mesothelioma among 379 rats, but no excess of lung tumours. The overall dose-response relation for lung cancer did not appear to be linear, consistent with the possibility of a threshold close to the Maximum Tolerated Dose. No insulation wool (glass, stone or slag) exposure group had a lung tumour rate that differed statistically significantly from the tumour rate for the respective concurrent control groups, sham-exposed to filtered air. There was no significant difference in the total tumour rates between the four insulation wool groups and the control animals, and no significant dose-response relation above the respective sham-exposed control tumour rates. The total lung tumour rates for rats in both chrysotile and crocidolite exposure groups were significantly raised. One animal in each asbestos-exposed group developed a mesothelioma

  19. Carcinogen risk assessment of chromium compounds

    SciTech Connect

    Gibb, H.J.; Chen, C.W.; Hiremath, C.B.

    1988-06-01

    Hexavalent chromium has been identified as a human carcinogen. Evidence to support this contention derives from epidemiologic, animal, and genotoxicity studies. Although workers exposed to both trivalent and hexavalent chromium have been shown to be at an excess risk of respiratory cancer, only hexavalent chromium has been shown to be carcinogenic in animals. Both hexavalent and trivalent chromium have been shown to be mutagenic, but the evidence for hexavalent chromium is somewhat stronger than that for trivalent chromium. The quantitative estimation of the cancer risk due to hexavalent chromium in the ambient air is calculated on the basis of lung-cancer mortality data for chromate production workers. The lifetime respiratory cancer risk due to 1 microgram/cu m) of hexavalent chromium in the ambient air is estimated to be 1.2 x .002 on the basis of Mancuso's data and 9.4 x .003 on the basis of the Braver et al. data.

  20. Studies on the conformation and dynamics of the C8-substituted guanine adduct of the carcinogen acetylaminofluorene; model for a possible Z-DNA modified structure.

    PubMed Central

    Neidle, S; Kuroda, R; Broyde, S; Hingerty, B E; Levine, R A; Miller, D W; Evans, F E

    1984-01-01

    The structure of an adduct between guanine and the carcinogen acetylaminofluorene has been examined in the solid state by X-ray crystallography, and in solution by NMR techniques. The observed conformations have been compared with predictions from energy calculations and their relevance to models of adducts with DNA has been examined. PMID:6504698

  1. MUTAGENIC AND CARCINOGENIC POTENCY OF EXTRACTS OF DIESEL AND RELATED ENVIRONMENTAL EMISSIONS: STUDY DESIGN, SAMPLE GENERATION, COLLECTION, AND PREPARATION (JOURNAL VERSION)

    EPA Science Inventory

    A major diesel emissions research program has been initiated by the US Environmental Protection Agency to assess the human health risk associated with increased use of diesel automobiles. This program is intended to establish the mutagenic and carcinogenic potency of complex orga...

  2. Comparative study of comprehensive gas chromatography-nitrogen chemiluminescence detection and gas chromatography-ion trap-tandem mass spectrometry for determining nicotine and carcinogen organic nitrogen compounds in thirdhand tobacco smoke.

    PubMed

    Ramírez, Noelia; Vallecillos, Laura; Lewis, Alastair C; Borrull, Francesc; Marcé, Rosa M; Hamilton, Jacqueline F

    2015-12-24

    Thirdhand tobacco smoke (THS) constitutes a poorly understood pathway of exposure of non-smokers, especially toddlers, to tobacco-related carcinogens. However, to date most of the carcinogens present in tobacco smoke have not been detected in THS and, therefore, the significance of THS health risk is still unknown. In this study, we have compared the performance of two analytical methods - one based on gas chromatography coupled to ion trap mass spectrometry detection (GC-IT-MS) and the other on comprehensive two-dimensional gas chromatography coupled to a nitrogen chemiluminescence detector (GC×GC-NCD) - for simultaneously determining, in settled house dust, the presence of 16 organic nitrogen carcinogens already detected in tobacco smoke. The target compounds included four aromatic amines, two nitrocompounds, eight N-nitrosamines and two tobacco-specific nitrosamines, as well as nicotine as a tobacco marker. Dust samples were extracted using in-cell clean up pressurized liquid extraction with silica as clean up sorbent and ethyl acetate as the organic solvent, with average recovery of 89%. Although GC-IT-MS, using chemical ionization with methanol and tandem MS, performed well, the optimized GC×GC-NCD gave lower limits of detection (from 4 to 22ngg(-1)) and better repeatability and reproducibility a low concentration levels (%RSD<8%) and, therefore, was applicable for determining these different groups of carcinogens without the need for derivatization prior to the GC analysis. The performance of the optimized PLE/GC×GC-NCD method was tested by quantifying the target compounds in house dust samples from smokers' and non-smokers' homes. The median carcinogen compounds detected was 3.8μgg(-1) and 1.1μgg(-1) in smokers' and non-smokers' house dust, respectively. In this study, we have detected highly carcinogenic aromatic amines and nitro compounds for the first time in settled house dust complementing the state of knowledge of THS composition and providing

  3. Studies on the mechanism of the acute and carcinogenic effects of N-nitrosodimethylamine on mink liver

    SciTech Connect

    Martino, P.E.; Diaz Gomez, M.I.; Tamayo, D.; Lopez, A.J.; Castro, J.A.

    1988-01-01

    Outbreaks of liver necrosis and liver hemangiosarcoma were detected in a mink breeding colony in Argentina. Analysis of the Minks' food revealed the presence of 2.6 ppm dimethylnitrosamine (NDMA) in it, apparently as a result of the addition of nitrite as preservative. Previous studies gave evidence of the particular susceptibility of minks to NDMA and other hepatic insults. The authors have determined several biochemical parameters known to correlate with NDMA hepatotoxic effects and compared with them those in rat liver. NDMA administration to both species resulted in the formation of reactive metabolites able to interact with liver DNA to give N/sup 7/-methylguanine and O/sup 6/-methylguanine adducts. Biotransformation of NDMA by liver slices to CO/sub 2/ was significantly lower in the mink than in the rat, whereas the covalent binding (CB) to nucleic acids was slightly lower than in the rat. Aminopyrine N-demethylase activity was also significantly less in mink than in rat liver. The CB of NDMA reactive metabolites to microsomal proteins was not significantly lower in mink as compared to the rat, and the same holds true for the biotransformation of NDMA to formaldehyde by microsomal preparations. Results suggest that the high susceptibility of minks to NDMA might be partially due to a decreased ability to detoxicate NDMA but also a higher intrinsic susceptibility of their liver cells to a given chemical insult.

  4. The Effect of Cigarette Smoking on Bladder Carcinogens in Man

    PubMed Central

    Kerr, W. K.; Barkin, M.; Levers, P. E.; Woo, S. K.-C.; Menczyk, Z.

    1965-01-01

    In the metabolism of the amino acid, tryptophan, certain products with the orthoaminophenol configuration are believed to act as topical carcinogens in the urinary bladder. In addition, a statistical relationship between cigarette smoking and bladder cancer has been established in recent years. Thirty metabolic studies are reported on six healthy male subjects when smoking and not smoking. Results revealed a consistent rise in carcinogenic metabolites of tryptophan when smoking (+ 50%), with a reciprocal fall in the end product, N'-methylnicotinamide (- 34%). Carcinogens fell and N'-methylnicotinamide rose when subjects stopped smoking. These metabolic studies confirm the statistical relationship between smoking and bladder cancer, and suggest that cigarette smoking blocks the normal metabolism of tryptophan, leading to the accumulation of carcinogenic metabolites. PMID:14306113

  5. Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

    PubMed Central

    Howard, P C; Eppley, R M; Stack, M E; Warbritton, A; Voss, K A; Lorentzen, R J; Kovach, R M; Bucci, T J

    2001-01-01

    Fumonisin B1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in BD IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F1 Nctr BR mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB1 in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FB1 in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15, 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F1 mice. PMID:11359696

  6. Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants

    SciTech Connect

    Persson, S.A.; Ahlberg, M.; Berghem, L.; Koenberg, E.N.; Nordberg, G.F.; Bergman, F.

    1988-04-01

    Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe/sub 2/O/sub 3/). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo(a)pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe/sub 2/O/sub 3/ coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash.

  7. Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants.

    PubMed Central

    Persson, S A; Ahlberg, M; Berghem, L; Könberg, E; Nordberg, G F; Bergman, F

    1988-01-01

    Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe2O3). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamsters were treated with suspensions of benzo[a]pyrene (BaP) or with suspensions on coal fly ash, oil fly ash, or Fe2O3 coated with BaP. The mass median aerodynamic diameters of the coal and oil fly ashes were 4.4 microns and 28 microns, respectively. Hamsters treated with oil fly ash showed a higher frequency of bronchiolar-alveolar hyperplasia than hamsters in the other treatment groups. Squamous dysplasia and squamous metaplasia were most frequent in animals treated with suspensions of BaP or BaP-coated particles. The earliest appearance of a tumor, the highest incidence of tumors, and the highest incidence of malignant tumors were observed in hamsters treated with oil fly ash coated with BaP. Squamous cell carcinoma and adenosquamous carcinoma were the most frequent malignant tumors. No malignant tumors and only few benign tumors were observed in hamsters instilled with suspensions of fly ash not coated with BaP. The present study gives no indication that coal fly ash could create more serious health problems than oil fly ash. Images FIGURE 3. FIGURE 4. PMID:3383816

  8. The use of oxytocin in liquid semen doses to reduce seasonal fluctuations in the reproductive performance of sows and improve litter parameters--a 2-year study.

    PubMed

    Duziński, Kamil; Knecht, Damian; Srodoń, Sebastian

    2014-04-01

    The objective of the present research was to eliminate seasonal fluctuations in year-round reproductive performance of sows and to improve litter parameters by administration of oxytocin into liquid semen insemination doses. A 2-year experiment was performed on crossbreed sows, Polish Large White × Polish Landrace, which were partitioned into two groups: control, insemination without any modification with 100 mL semen doses and oxytocin, insemination with 100 mL semen doses to which 5 IU of oxytocin was added just before insemination. A total of 10,486 inseminations were made. The farrowing rate and obtained litter parameters, including the effect of season, were analyzed. For each litter, the following factors were defined: average litter size, percentage of fetal death and mummified piglets, average piglet birth weight, percentage of piglet mortality, fecundity index, average number of piglets weaned, weaned piglet weight, and daily gain. Sows presented a positive reaction to the experimental factor. A statistically higher farrowing rate for oxytocin group in summer and autumn seasons was confirmed (P ≤ 0.01). Regardless of the season, a higher average litter size was observed in the oxytocin group with the most evident differences for winter, spring (P ≤ 0.01), and summer (P ≤ 0.05). The effect of oxytocin on the percentage of fetal death and mummified piglets born was not confirmed statistically except for winter. Analyzing the fecundity index, higher values were obtained for the oxytocin group in all seasons (P ≤ 0.01), including the lowest difference between groups for winter (51.43) and the highest for summer (100.61). A higher average birth piglet weight and weaned piglet weight were recorded for the oxytocin group in all seasons. The highest differences in birth piglet weight between groups were noted for spring (0.22 kg; P ≤ 0.01) and winter (0.17 kg; P ≤ 0.05) and in weaned piglet weight for winter and spring (0.58 kg and 0.52 kg; for

  9. Effects of SO2 or NOx on toxic and genotoxic properties of chemical carcinogens. I. In vitro studies.

    PubMed

    Pool, B L; Janowsky, I; Klein, P; Klein, R G; Schmezer, P; Vogt-Leucht, G; Zeller, W J

    1988-07-01

    This paper describes in vitro studies on the effects of environmental pollutants (SO2/NOx) in biological systems. Basic physical, chemical and biochemical parameters were analyzed to establish the rate of SO2/NOx absorption by the culture medium. It was shown that the pH remains constant for 24 h of exposure to gas concentrations up to 50 p.p.m. The concentration of ions resulting from absorption of each pollutant in the liquid phase is dependent on their concentration in the gas phase and on exposure time. Short exposure times and high gas dosages resulted in similar doses in the medium as long exposure periods and low gas dosages. The activities of a human serum standard (alkaline phosphatase, ALP; aspartate amino transferase, AST; alanine amino transferase, ALT; gamma-glutamyltransferase, gamma-GT; lactate dehydrogenase, LDH) were determined after gaseous exposure to SO2 and NOx. The results revealed a distinct decrease in the activity of LDH after 1, 3 and 5 h exposure to 200 p.p.m. SO2. The effects of the pollutants were assayed in vitro using fetal hamster lung cells (FHLC), rat hepatocytes and the cell line CO60. For the determination of toxic effects, it was shown that the plating efficiency was a more sensitive parameter than the assay for trypan blue exclusion. Toxicity indicated as an increase of LDH leakage was not observed from FHLC in culture. Instead, a decrease of LDH was found following SO2 exposition. This decrease was similar to that observed for the human serum standard. The induction of DNA single-strand breaks was determined as a measure of genotoxic effects. SO2 application decreased the rate of DNA single-strand breaks induced by N-nitroso-acetoxymethyl-methylamine in both FHLC and in rat hepatocytes. SO2 or NOx treatment of CO60 cells for 1 h did not result in the induction of DNA amplification. HSO3- added directly to the medium as the sodium salt, however, distinctly induced the amplification of SV40 DNA. The amplification rates induced

  10. Potential carcinogenic effects of cigarette smoke and Swedish moist snuff on pancreas: a study using a transgenic mouse model of chronic pancreatitis.

    PubMed

    Song, Zhigang; Bhagat, Govind; Quante, Michael; Baik, Gwang Ho; Marrache, Frederic; Tu, Shui Ping; Zhao, Chun-Mei; Chen, Duan; Dannenberg, Andrew J; Wang, Timothy C

    2010-03-01

    The risk of pancreatic cancer is increased in both Snus (the Swedish variant of oral smokeless tobacco) users and, to a greater extent, in cigarette smokers. Concurrent chronic pancreatitis further increases the risk in cigarette smokers. Little is known about the mechanism by which cigarette smoke or Snus increase the risk of pancreatic cancer in individuals with chronic pancreatitis. This study examined the carcinogenic effects of an aqueous extract of cigarette smoke (tobacco smoke, TS) or Snus in an Elastase-IL-1beta transgenic mouse model of chronic pancreatitis. Both transgenic and wild-type (WT) mice were fed diluted TS water or Snus-containing diet for up to 15 months, and monitored for phenotypic and molecular changes in the pancreas. Both TS- and Snus-treated Elastase-IL-1beta mice, but not WT mice, developed significant pancreatic ductal epithelial flattening and severe glandular atrophy compared with untreated transgenic mice. Ductal epithelial cells displayed a high proliferative index, minimal apoptosis, and induction of COX-2 in the setting of chronic inflammation. Up-regulation of TNF-alpha correlated with the onset of severe glandular atrophy. In comparison with Snus-treated mice, TS-Elastase-IL-1beta mice had an earlier onset and a greater extent of phenotypic changes, which were associated with up-regulation of TNF-alpha and increased expression of IL-6, TGF-beta, and SDF-1. Collectively, these findings provide new insights into the mechanism by which tobacco products are likely to promote carcinogenesis in the setting of chronic pancreatitis. PMID:20065943

  11. Summary of carcinogenic potency and positivity for 492 rodent carcinogens in the carcinogenic potency database.

    PubMed Central

    Gold, L S; Slone, T H; Bernstein, L

    1989-01-01

    A tabulation of carcinogenic potency (TD50) by species for 492 chemicals that induce tumors in rats or mice is presented. With the use of the Carcinogenic Potency Database, experimental results are summarized by indicating in which sex-species groups the chemical was tested and the respective evaluations of carcinogenicity. A comparison of three summary measures of TD50 for chemicals with more than one positive experiment per species shows that the most potent TD50 value is similar to measures that average values or functions of values. This tabulation can be used to investigate associations between rodent potency and other factors such as mutagenicity, teratogenicity, chemical structure, and human exposure. PMID:2707207

  12. Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide.

    PubMed Central

    Ashby, J.; Styles, J. A.; Anderson, D.

    1977-01-01

    The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced. PMID:337998

  13. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    PubMed Central

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  14. Predictors (0-10 Months) of Psychopathology at Age 1 1/2 Years--A General Population Study in the Copenhagen Child Cohort CCC 2000

    ERIC Educational Resources Information Center

    Skovgaard, A. M.; Olsen, E. M.; Christiansen, E.; Houmann, T.; Landorph, S. L.; Jorgensen, T.

    2008-01-01

    Background: Epidemiological studies of mental health problems in the first years of life are few. This study aims to investigate infancy predictors of psychopathology in the second year of life. Methods: A random general population sample of 210 children from the Copenhagen Child Birth Cohort CCC 2000 was investigated by data from National Danish…

  15. New clues on carcinogenicity-related substructures derived from mining two large datasets of chemical compounds.

    PubMed

    Golbamaki, Azadi; Benfenati, Emilio; Golbamaki, Nazanin; Manganaro, Alberto; Merdivan, Erinc; Roncaglioni, Alessandra; Gini, Giuseppina

    2016-04-01

    In this study, new molecular fragments associated with genotoxic and nongenotoxic carcinogens are introduced to estimate the carcinogenic potential of compounds. Two rule-based carcinogenesis models were developed with the aid of SARpy: model R (from rodents' experimental data) and model E (from human carcinogenicity data). Structural alert extraction method of SARpy uses a completely automated and unbiased manner with statistical significance. The carcinogenicity models developed in this study are collections of carcinogenic potential fragments that were extracted from two carcinogenicity databases: the ANTARES carcinogenicity dataset with information from bioassay on rats and the combination of ISSCAN and CGX datasets, which take into accounts human-based assessment. The performance of these two models was evaluated in terms of cross-validation and external validation using a 258 compound case study dataset. Combining R and H predictions and scoring a positive or negative result when both models are concordant on a prediction, increased accuracy to 72% and specificity to 79% on the external test set. The carcinogenic fragments present in the two models were compared and analyzed from the point of view of chemical class. The results of this study show that the developed rule sets will be a useful tool to identify some new structural alerts of carcinogenicity and provide effective information on the molecular structures of carcinogenic chemicals. PMID:26986491

  16. EVALUATION OF THE CARCINOGENICITY OF UNLEADED GASOLINE

    EPA Science Inventory

    In the document the likelihood that unleaded gasoline vapors are carcinogenic to humans is evaluated. From carcinogenicity data in animals, an estimate is made of the magnitude of cancer risk a person would experience, under the assumption that gasoline vapors are carcinogenic. A...

  17. Working Memory Arrest in Children with High-Functioning Autism Compared to Children with Attention-Deficit/Hyperactivity Disorder: Results from a 2-Year Longitudinal Study

    ERIC Educational Resources Information Center

    Andersen, Per N.; Skogli, Erik W.; Hovik, Kjell T.; Geurts, Hilde; Egeland, Jens; Øie, Merete

    2015-01-01

    The aim of this study was to analyse the development of verbal working memory in children with high-functioning autism compared to children with attention-deficit/hyperactivity disorder and typically developing children. A total of 34 children with high-functioning autism, 72 children with attention-deficit/hyperactivity disorder and 45 typically…

  18. Prospective Analysis of a New Bone Graft in Lumbar Interbody Fusion: Results of a 2- Year Prospective Clinical and Radiological Study

    PubMed Central

    Raskin, Yannic

    2015-01-01

    Background This study examined the efficacy and safety of bone graft material ABM/P-15 (iFACTOR) for use in posterior lumbar interbody fusion. ABM/P-15 has been used safely for more than a decade in dental applications. Methods Forty patients underwent PLIF surgery, with each patient as control. Assessments up to 24 months included radiographs, CT scan, VAS, and ODI. Primary success criteria were fusion and safety. Results Intra-cage bridging bone occurred earlier with ABM/P-15 than autograft (97.73% vs. 59.09% at 6 months). On average pain decreased 29 points and function improved 43 points. Radio dense material outside the disk space occurred more frequently with ABM/P-15 than autograft, without clinical consequence. Conclusions This study suggests that ABM/P-15 has equal or greater efficacy at 6 and 12 months. Pain improvements exceeded success criteria at all time points. Functional improvement exceeded success criteria at all time points. Clinical Relevance This study explores the safety and efficacy of an osteobiologic peptide enhanced bone graft material as a viable alternative to autograft and its attendant risks. PMID:25709887

  19. Etiological Role and Repeated Infections of Sapovirus among Children Aged Less than 2 Years in a Cohort Study in a Peri-urban Community of Peru.

    PubMed

    Liu, Xiaofang; Jahuira, Helena; Gilman, Robert H; Alva, Alicia; Cabrera, Lilia; Okamoto, Michiko; Xu, Hang; Windle, Henry J; Kelleher, Dermot; Varela, Marco; Verastegui, Manuela; Calderon, Maritza; Sanchez, Gerardo; Sarabia, Vanessa; Ballard, Sarah B; Bern, Caryn; Mayta, Holger; Crabtree, Jean E; Cama, Vitaliano; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-01

    Human sapovirus has been shown to be one of the most important etiologies in pediatric patients with acute diarrhea. However, very limited data are available about the causative roles and epidemiology of sapovirus in community settings. A nested matched case-control study within a birth cohort study of acute diarrhea in a peri-urban community in Peru from 2007 to 2010 was conducted to investigate the attributable fraction (AF) and genetic diversity of sapovirus. By quantitative reverse transcription-real-time PCR (qPCR) sapovirus was detected in 12.4% (37/299) of diarrheal and 5.7% (17/300) of nondiarrheal stools (P = 0.004). The sapovirus AF (7.1%) was higher in the second year (13.2%) than in the first year (1.4%) of life of children. Ten known genotypes and one novel cluster (n = 5) within four genogroups (GI, GII, GIV, and GV) were identified by phylogenetic analysis of a partial VP1 gene. Further sequence analysis of the full VP1 gene revealed a possible novel genotype, tentatively named GII.8. Notably, symptomatic reinfections with different genotypes within the same (n = 3) or different (n = 5) genogroups were observed in eight children. Sapovirus exhibited a high attributable burden for acute gastroenteritis, especially in the second year of life, of children in a Peruvian community. Further large-scale studies are needed to understand better the global burden, genetic diversity, and repeated infections of sapovirus. PMID:27076657

  20. BINDING OF CHEMICAL CARCINOGENS AND MUTAGENS TO RAT HEMOGLOBIN

    EPA Science Inventory

    The alkylation of hemoglobin is a proposed dose monitor for chemical carcinogens and mutagens. The binding of fifteen chemical carcinogens and mutagens to rat hemoglobin was determined. Direct acting carcinogens and indirect acting carcinogens including aromatic amines, halogenat...

  1. Efficacy and safety of finasteride therapy for benign prostatic hyperplasia: results of a 2-year randomized controlled trial (the PROSPECT study). PROscar Safety Plus Efficacy Canadian Two year Study.

    PubMed Central

    Nickel, J C; Fradet, Y; Boake, R C; Pommerville, P J; Perreault, J P; Afridi, S K; Elhilali, M M

    1996-01-01

    OBJECTIVE: To evaluate the efficacy and safety of 2 years' treatment of moderate benign prostatic hyperplasia (BPH) with finasteride. DESIGN: Double-blind, parallel-group, placebo-controlled, multicentre, prospective randomized study. SETTING: Outpatient care in 28 centres across Canada. PARTICIPANTS: Men aged 45 to 80, in good health, with moderate BPH and no evidence of prostate cancer. A total of 613 men were entered into the study; 472 completed the 2 years of treatment. INTERVENTION: After 1 month of receiving a placebo (run-in period), patients were given either finasteride (5 mg/d) or a placebo for 2 years. OUTCOME MEASURES: Efficacy: changes from baseline in BPH symptom scores, maximum urinary flow rates and prostate volume. Safety: onset, course and resolution of all adverse events during the treatment period. RESULTS: In the efficacy analyses the mean BPH symptom scores decreased 2.1 points (from 15.8 to 13.7) in the finasteride group, as compared with a decrease of 0.7 points (from 16.6 to 15.9) in the placebo group (P < or = 0.01). The maximum urinary flow rate increased by a mean of 1.4 mL/s (from 11.1 to 12.5 mL/s) in the finasteride group, as compared with an increase of 0.3 mL/s (from 10.9 to 11.2 mL/s) in the placebo group (p < or = 0.01). The mean prostate volume decreased by 21% (from a mean volume of 44.1 cm3 at baseline) in the treatment group; it increased by 8.4% (from a mean volume of 45.8 cm3 at baseline) in the placebo group (p < or = 0.01). In the safety analysis, the proportion of patients who experienced any adverse event was similar in the two groups (81.0% in the treatment group and 81.2% in the placebo group). However, the incidence of adverse events related to sexual dysfunction were significantly higher in the finasteride group than in the placebo group (ejaculation disorder 7.7% v. 1.7% and impotence 15.8% v. 6.3%; p < or = 0.01 for both parameters). CONCLUSION: Finasteride is a well-tolerated and effective alternative to watchful

  2. Predicting adolescent problematic online game use from teacher autonomy support, basic psychological needs satisfaction, and school engagement: a 2-year longitudinal study.

    PubMed

    Yu, Chengfu; Li, Xian; Zhang, Wei

    2015-04-01

    Problematic online game use (POGU) has become a serious global public health concern among adolescents. However, its influencing factors and mediating mechanisms remain largely unknown. This study provides the first longitudinal design to test stage-environment fit theory empirically in POGU. A total of 356 Chinese students reported on teacher autonomy support, basic psychological needs satisfaction, school engagement, and POGU in the autumn of their 7th-9th grade years. Path analyses supported the proposed pathway: 7th grade teacher autonomy support increased 8th grade basic psychological needs satisfaction, which in turn increased 9th grade school engagement, which ultimately decreased 9th grade POGU. Furthermore, 7th grade teacher autonomy support directly increased 9th grade school engagement, which in turn decreased 9th grade POGU. These findings suggest that teacher autonomy support is an important protective predictor of adolescent POGU, and basic psychological needs satisfaction and school engagement are the primary mediators in this association. PMID:25803769

  3. Serum antibody responses to pneumococcal colonization in the first 2 years of life: results from an SE Asian longitudinal cohort study.

    PubMed

    Turner, P; Turner, C; Green, N; Ashton, L; Lwe, E; Jankhot, A; Day, N P; White, N J; Nosten, F; Goldblatt, D

    2013-12-01

    Assessment of antibody responses to pneumococcal colonization in early childhood may aid our understanding of protection and inform vaccine antigen selection. Serum samples were collected from mother-infant pairs during a longitudinal pneumococcal colonization study in Burmese refugees. Maternal and cord sera were collected at birth and infants were bled monthly (1–24 months of age). Nasopharyngeal swabs were taken monthly to detect colonization. Serum IgG titres to 27 pneumococcal protein antigens were measured in 2624 sera and IgG to dominant serotypes (6B, 14, 19F, 19A and 23F) were quantified in 864 infant sera. Antibodies to all protein antigens were detect ablein maternal sera. Titres to four proteins (LytB, PcpA, PhtD and PhtE) were significantly higher in mothers colonized by pneumococci at delivery. Maternally-derived antibodies to PiuA and Spr0096 were associated with delayed pneumococcal acquisition in infants in univariate,but not multivariate models. Controlling for infant age and previous homologous serotype exposure, nasopharyngeal acquisition of serotypes 19A, 23F, 14 or 19F was associated significantly with a ≥2-fold antibody response to the homologous capsule (OR 12.84, 7.52,6.52, 5.33; p <0.05). Acquisition of pneumococcal serotypes in the nasopharynx of infants was not significantly associated with a ≥2-fold rise in antibodies to any of the protein antigens studied. In conclusion, nasopharyngeal colonization in young children resulted in demonstrable serum IgG responses to pneumococcal capsules and surface/virulence proteins. However, the relationship between serum IgG and the prevention of, or response to, pneumococcal nasopharyngeal colonization remains complex. Mechanisms other than serum IgG are likely to have a role but are currently poorly understood. PMID:24255996

  4. The Prospective Intraoperative and Perioperative Ophthalmic ImagiNg with Optical CoherEncE TomogRaphy (PIONEER) Study: 2-year Results

    PubMed Central

    Ehlers, Justis P.; Dupps, William J.; Kaiser, Peter K.; Goshe, Jeff; Singh, Rishi P.; Petkovsek, Dan; Srivastava, Sunil K.

    2014-01-01

    Purpose To evaluate the feasibility, safety, and utility of intraoperative optical coherence tomography (OCT) for use during ophthalmic surgery. Design Prospective, consecutive, case series Methods A prospective, single-center, consecutive, case series was initiated to assess intraoperative OCT in ophthalmic surgery. Intraoperative scanning was performed with a microscope mounted spectral domain OCT system. Disease specific or procedure-specific imaging protocols (e.g., scan type, pattern, size, orientation, density) were utilized for anterior and posterior segment applications. A surgeon feedback form was recorded as part of the study protocol to answer specific questions regarding intraoperative OCT utility immediately after the surgical procedure was completed. Results During the first 24 months of the PIONEER study, 531 eyes were enrolled (275 anterior segment cases and 256 posterior segment surgical cases). Intraoperative OCT imaging was obtained in 518 of 531 eyes (98%). Surgeon feedback indicated that intraoperative OCT informed surgical decision-making and altered surgeon understanding of underlying tissue configurations in 69/144 (48%) lamellar keratoplasty cases and 63/146 (43%) membrane peeling procedures. The most common anterior segment surgical procedure was descemet stripping automated endothelial keratoplasty (DSAEK, n = 135). Vitrectomy with membrane peeling was the most common procedure for posterior segment surgery (n = 154). The median time that surgery was paused to perform intraoperative OCT was 4.9 minutes per scan session. No adverse events were specifically attributed to intraoperative OCT scanning during the procedure. Conclusions Intraoperative OCT is feasible for numerous anterior and posterior segment ophthalmic surgical procedures. A microscope mounted intraoperative OCT system provided efficient imaging during operative procedures. The information gained from intraoperative OCT may impact surgical decision-making in a high frequency

  5. Inhalation carcinogenicity of dichloromethane in rats and mice.

    PubMed

    Aiso, Shigetoshi; Take, Makoto; Kasai, Tatsuya; Senoh, Hideki; Umeda, Yumi; Matsumoto, Michiharu; Fukushima, Shoji

    2014-07-01

    The carcinogenicity of inhaled dichloromethane (DCM) was examined by exposing groups of 50 F344/DuCrj rats and 50 Crj: BDF1 mice of both sexes to 0, 1000, 2000, or 4000 ppm (w/w) DCM-containing aerosol for 2 years. Inhalation of DCM resulted in increased incidences of subcutis fibromas, mammary gland fibroadenoma, and peritoneum mesotheliomas in male rats; mammary gland fibroadenomas in female rats; and bronchiolar-alveolar adenomas and carcinomas in the lung and hepatocellular adenomas and carcinomas in male and female mice. These results clearly indicate that inhaled DCM is carcinogenic in F344/DuCrj (SPF) rats and Crj: BDF1 (SPF) mice. PMID:24909451

  6. The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study

    PubMed Central

    Jevšnik, Monika; Steyer, Andrej; Pokorn, Marko; Mrvič, Tatjana; Grosek, Štefan; Strle, Franc; Lusa, Lara; Petrovec, Miroslav

    2016-01-01

    Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9.9%, 95% CI: 6–15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3–13.3%) and AB (20/308, 6.5%, 95% CI: 4.0–9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1–99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9–75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3–61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4–5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02–3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%. Trial Registration: ClinicalTrials.gov NCT00987519 PMID:27171141

  7. Decreased use of glucocorticoids in biological-experienced patients with rheumatoid arthritis who initiated intravenous abatacept: results from the 2-year ACTION study

    PubMed Central

    Alten, Rieke; Nüßlein, Hubert; Galeazzi, Mauro; Lorenz, Hanns-Martin; Nurmohamed, Michael T; Bensen, William G; Burmester, Gerd R; Peter, Hans-Hartmut; Pavelka, Karel; Chartier, Mélanie; Poncet, Coralie; Rauch, Christiane; Elbez, Yedid; Le Bars, Manuela

    2016-01-01

    Introduction Prolonged glucocorticoid use may increase the risk of adverse safety outcomes, including cardiovascular events. The European League Against Rheumatism and the Canadian Rheumatology Association advise tapering glucocorticoid dose as rapidly as clinically feasible. There is a paucity of published data on RA that adequately describe concomitant treatment patterns. Methods ACTION (AbataCepT In rOutiNe clinical practice) is a non-interventional cohort study of patients from Europe and Canada that investigated the long-term retention of intravenous abatacept in clinical practice. We assessed concomitant glucocorticoids in patients with established RA who had participated in ACTION and received ≥1 biological agent prior to abatacept initiation. Results The analysis included 1009 patients. Glucocorticoids were prescribed at abatacept initiation in 734 (72.7%) patients at a median 7.5 mg/day dose (n=692). Of the patients who remained on abatacept at 24 months, 40.7% were able to decrease their dose of glucocorticoids, including 26.9% who decreased their dose from >5 mg/day to ≤5 mg/day. Conclusion Reduction and/or cessation of glucocorticoid therapy is possible with intravenous abatacept in clinical practice. PMID:26925253

  8. Personal and demographic factors and change of subjective indoor air quality reported by school children in relation to exposure at Swedish schools: a 2-year longitudinal study.

    PubMed

    Wang, Juan; Smedje, Greta; Nordquist, Tobias; Norbäck, Dan

    2015-03-01

    This paper studies changes in subjective indoor air quality (SIAQ) among school children and relates these data to repeated exposure measurements during a two-year follow-up period. Data on SIAQ and demographic information were gathered by a questionnaire sent to 1476 primary and secondary school pupils in 39 randomly selected schools at baseline and after two years (follow-up). Exposure measurements were applied after questionnaire data were collected at baseline and follow-up in approximately 100 classrooms. The arithmetic mean values for baseline and follow-up were: for indoor air temperature 23.6°C and 21.8°C and for outdoor air flow rate 5.4 L/s and 7.9L/s. Older children, those with atopy at baseline, and those in larger schools reported impaired SIAQ during follow-up. Installation of new ventilation systems, higher personal air flow rate and air exchange rate, and better illumination were associated with improved SIAQ. Higher CO2 levels were associated with impaired SIAQ. In conclusion, sufficient ventilation and illumination in classrooms are essential for the perception of good indoor air quality. PMID:25486639

  9. Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

    PubMed Central

    Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

    2008-01-01

    Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

  10. The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up.

    PubMed

    Lambrechts, Danielle A J E; de Kinderen, Reina J A; Vles, Hans S H; de Louw, Anton J; Aldenkamp, Albert P; Majoie, Marian J M

    2015-10-01

    The present study assessed the long-term (i.e., 24months) efficacy of the ketogenic diet (KD) as an add-on therapy in children with refractory epilepsy, with focus on seizure frequency, seizure severity, and tolerability. Most patients were treated with the MCT-diet. At one and two years, 33% and 23%, respectively, of the 48 included patients were still on the KD. After three months, one year, and two years of treatment, 16.7% of the patients were responders. The highest responder rate (i.e., 22.9%) was seen at six and nine months of treatment. Of the fifteen patients with seizure clusters during baseline, 60% were responders after three months when looking at cluster reduction and most of them were not responders for the total seizure frequency. From three months of treatment onwards, most of the patients had a relevant decrease in seizure severity which was mainly related to the most severe seizure type. Gastrointestinal dysfunction was often reported, especially in the first six weeks of treatment. Growth deceleration was present in 30% of the patients, and weight reduction in 15%. Improved arousal was mentioned in 30% of patients. No patients developed ECG abnormalities or kidney stones. Increase in lipid profile was rare. The KD is an effective therapy for children with therapy-resistant epilepsy. Effectiveness is reflected in the reduction of seizure frequency as well as in the reduction of seizure severity. After 6months of treatment, it is obvious which patients are responders and tolerate the treatment well. Most of these patients will continue to benefit from the KD for a longer time. Long-term use of the diet was well tolerated. PMID:26301622

  11. In situ measured and simulated seasonal freeze-thaw cycle: A 2-year comparative study between layered and homogeneous field soil profiles

    NASA Astrophysics Data System (ADS)

    Cheng, Q.; Sun, Y.; Jones, S. B.; Vasilyev, V. I.; Popov, V. V.; Wang, G.; Zheng, L.

    2014-11-01

    Annual freeze-thaw cycles of soil significantly impact agricultural and ecosystem services in cold regions. For advancing our understanding of freeze-thaw process, both improved measurements and simulations of coupled-heat-water-transfer (CHWT) phenomenon are needed under different field conditions. This paper focused on a comparative study between a CHWT-model simulation versus in situ measurements of liquid soil water content (LSWC) and soil temperature (ST) at two agricultural field sites. The first site consisted of a layered soil profile with sandy silt loam (0-60 cm) and clay loam (60-130 cm) layers, and the other site was a uniform sand profile (0-110 cm). Measurements were made over two winters between 2011 and 2013, i.e. the first winter is 2011-2012 (year 1) and the second winter is 2012-2013 (year 2), in the northeast of China employing an access-tube dielectric sensor combined with a temperature measurement array. During the freezing period of the year 1 winter, the soil freezing characteristic curves (SFCCs) were determined in situ in relation to the site-specific data of LSWC and ST and subsequently used for the model calibration. For the thawing process of year 1 and the freeze-thaw process of year 2, the resulting ST simulation time series were well-correlated with field measurements. In terms of the resulting LSWC, the numerical simulations also correlated well (R2 > 0.895, RMSE < 0.0381 cm3 cm-3) with the in situ observations of freezing and quasi-steady-state conditions at depths of 50- and 100-cm. The reasons for relatively reduced agreement between simulated and measured LSWC during the thawing stage (i.e., R2 > 0.702, RMSE < 0.0468 cm3 cm-3) are discussed. The resulting time series simulations confirm the model's capability for describing freeze- and thaw-front migration in layered and homogeneous freezing soils.

  12. Change in Care Dependency and Nursing Care Problems in Nursing Home Residents with and without Dementia: A 2-Year Panel Study

    PubMed Central

    2015-01-01

    Over time, chronic conditions like dementia can lead to care dependency and nursing care problems, often necessitating nursing home admission. This panel study (2012–2014) aims to explore changes in care dependency and nursing care problems (incontinence, malnutrition, decubitus, falls and restraints) in residents with and without dementia over time. In total, nine Austrian nursing homes participated, including 258 residents (178 with, 80 without dementia) who completed all five measurements. Data were collected with the International Prevalence Measurement of Care Problems questionnaire, the Care Dependency Scale and the Mini-Mental State Examination-2. Repeated measures ANOVA and crosstabs were used to analyse changes. The results showed that care dependency in dementia residents increased significantly for all 15 items of the Care Dependency Scale, with the highest increase being residents’ day-/night pattern, contact with others, sense of rules/values and communication. In contrast, care dependency in residents without dementia increased for four of the 15 items, with the highest increase being for continence, followed by getting (un)dressed. With respect to the assessed nursing care problems, residents with dementia and those without only differed significantly in terms of an increase in urinary- (12.3% vs. 14.2%), fecal- (17.4% vs. 10%), and double incontinence (16.7% vs. 11.9%). The results indicated that residents with dementia experienced increased care dependency in different areas than residents without dementia. Furthermore, residents with dementia experienced a lower increase in urinary incontinence but a higher increase in fecal- and double incontinence. These results help professionals to identify areas for improvement in dementia care. PMID:26513358

  13. Carcinogenicity of methyl-tertiary butyl ether in gasoline.

    PubMed

    Mehlman, Myron A

    2002-12-01

    Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks

  14. Carcinogenicity of 1,3-butadiene.

    PubMed Central

    Melnick, R L; Shackelford, C C; Huff, J

    1993-01-01

    1,3-Butadiene, a high-production volume chemical used largely in the manufacture of synthetic rubber, is a multiple organ carcinogen in rats and mice. In inhalation studies conducted in mice by the National Toxicology Program, high rates of early lethal lymphomas occurring at exposure levels of 625 ppm or higher reduced the development and expression of later developing tumors at other sites. Use of survival-adjusted tumor rates to account for competing risk factors provided a clearer indication of the dose responses for 1,3-butadiene-induced neoplasms. An increase in lung tumors in female mice was observed at exposure concentrations as low as 6.25 ppm, the lowest concentration ever used in a long-term carcinogenicity study of this gas. Human exposures to 1,3-butadiene by workers employed at facilities that produce this chemical and at facilities that produce styrene-butadiene rubber have been measured at levels higher than those that cause cancer in animals. Furthermore, epidemiology studies have consistently revealed associations between occupational exposure to 1,3-butadiene and excess mortality due to lymphatic and hematopoietic cancers. In response to the carcinogenicity findings for 1,3-butadiene in animals and in humans, the Occupational Safety and Health Administration has proposed lowering the occupational exposure standard for this chemical from 1000 ppm to 2 ppm. Future work is needed to understand the mechanisms of tumor induction by 1,3-butadiene; however, the pursuit of this research should not delay the reduction of human exposure to this chemical. PMID:8354171

  15. Report on carcinogens monograph on cumene.

    PubMed

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers. PMID

  16. Vagus nerve stimulation therapy: 2-year prospective open-label study of 40 subjects with refractory epilepsy and low IQ who are living in long-term care facilities.

    PubMed

    Huf, Roger L; Mamelak, Adam; Kneedy-Cayem, Kara

    2005-05-01

    Treating seizures among patients with mental retardation/developmental disabilities (MR/DD) is difficult owing in large part to the presence of additional comorbidities and the resulting need for polytherapy. Therefore, a nonpharmacological treatment option is needed for this population. This prospective, open-label study documented the long-term outcome of 40 low-IQ (<70) patients living in long-term care facilities who received vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy. Subjects were seen every 1 to 3 months by their neurologist (R.H.). Seizure frequency, antiepileptic medication, and quality-of-life information were documented preimplantation and quarterly thereafter through 2 years. The surgery and therapy were well tolerated. Seizures were reduced by at least 50% for 11 subjects. Antiepileptic medications were reduced from 3.3 per subject at baseline to an average of 2.3 per subject after 2 years. According to caregiver reports, overall quality of life improved for the majority of subjects; also, using the Client Development Evaluation Report (CDER), statistically significant improvements were reported at both 1 and 2 years in attention span, word usage, clarity of speech, standing balance, washing dishes, and household chores. VNS is a viable treatment option for low-IQ patients with pharmacoresistant epilepsy who are living in long-term care facilities. PMID:15820352

  17. Evaluation of the potential carcinogenicity of benzo(k)fluoranthene. Final report

    SciTech Connect

    Not Available

    1988-06-01

    Benzo(k)fluoranthene is not classifiable as a human carcinogen, and is, therefore, placed in weight-of-evidence Group D under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Inadequate, and the evidence from human studies is No Data. Due to the inadequacy or lack of human and animal data, benzo(k)fluoranthene could not be assigned a potency factor (F), could not be placed in a potency group, nor could it receive a hazard ranking for the purposes of RQ adjustment. Therefore, no RQ can be assigned based on potential carcinogenicity. Other primary criteria must be used for assigning RQ's.

  18. Evaluation of the potential carcinogenicity of coke oven emissions. Final report

    SciTech Connect

    1988-06-01

    Coke oven emissions are known human carcinogens, classified as weight-of-evidence Group A under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Sufficient. The potency factor (F) for coke oven emissions are estimated to be 1.53 (mg/kg/day)(-1), placing it in potency group 2 according to the CAG`s methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, coke oven emissions are assigned a HIGH hazard ranking.

  19. Evaluation of the potential carcinogenicity of DDT (50-29-3). Final report

    SciTech Connect

    Not Available

    1988-06-01

    DDT is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment. Evidence on potential carcinogenicity from animal studies is Sufficient. and the evidence from human studies is Inadequate. The potency factor (F) for DDT is estimated to be 5.58 (mg/kg/day)(-1), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens. Combining the weight-of-evidence group and the potency group, DDT is assigned a MEDIUM hazard ranking.

  20. Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds.

    PubMed

    Behl, Mamta; Stout, Matthew D; Herbert, Ronald A; Dill, Jeffrey A; Baker, Gregory L; Hayden, Barry K; Roycroft, Joseph H; Bucher, John R; Hooth, Michelle J

    2015-07-01

    Occupational exposure to cobalt is of widespread concern due to its use in a variety of industrial processes and the occurrence of occupational disease. Due to the lack of toxicity and carcinogenicity data following exposure to cobalt, and questions regarding bioavailability following exposure to different forms of cobalt, the NTP conducted two chronic inhalation exposure studies in rats and mice, one on soluble cobalt sulfate heptahydrate, and a more recent study on insoluble cobalt metal. Herein, we compare and contrast the toxicity profiles following whole-body inhalation exposures to these two forms of cobalt. In general, both forms were genotoxic in the Salmonella T98 strain in the absence of effects on micronuclei. The major sites of toxicity and carcinogenicity in both chronic inhalation studies were the respiratory tract in rats and mice, and the adrenal gland in rats. In addition, there were distinct sites of toxicity and carcinogenicity noted following exposure to cobalt metal. In rats, carcinogenicity was observed in the blood, and pancreas, and toxicity was observed in the testes of rats and mice. Taken together, these findings suggest that both forms of cobalt, soluble and insoluble, appear to be multi-site rodent carcinogens following inhalation exposure. PMID:25896363

  1. 4,4'-Methylenebis (2-chloroaniline): an unregulated carcinogen

    SciTech Connect

    Ward, E.; Smith, A.B.; Halperin, W.

    1987-01-01

    4,4'-Methylenebis (2-chloroaniline) (MBOCA) is a confirmed animal carcinogen. It is used commercially as a curing agent for polymers containing isocyanate. There are no adequate studies documenting a carcinogenic risk for MBOCA in humans; however, studies in rats and dogs have shown that MBOCA is a carcinogen. Also, MBOCA is structurally similar to aromatic amines, which cause bladder cancer in workers with occupational exposure. Manufacture of MBOCA in the United States ceased in 1979. However, estimates of the number of workers potentially exposed range from 1,400 to 33,000 in the manufacture of MBOCA-cured products. Presently, there are no federal regulations limiting occupational exposure to MBOCA. An occupational standard for MBOCA proposed by the Occupational Safety and Health Administration was remanded by the Third Circuit Court of Appeals on procedural grounds in 1974. NIOSH recommended in 1978 that MBOCA be treated as a potential human carcinogen and that worker exposure be controlled so that it does not exceed 3 micrograms/m3 of air determined as a time-weighted average concentration for up to a 10-hour workshift (the lowest level that can be reliably measured). In this paper, we will review the literature in regard to MBOCA's carcinogenicity, describe industrial use and extent of worker exposure, and review MBOCA's status in relation to occupational regulations in the United States and abroad. 51 references.

  2. N-Methyl-N-nitrosourea as a mammary carcinogenic agent.

    PubMed

    Faustino-Rocha, Ana I; Ferreira, Rita; Oliveira, Paula A; Gama, Adelina; Ginja, Mário

    2015-12-01

    The administration of chemical carcinogens is one of the most commonly used methods to induce tumors in several organs in laboratory animals in order to study oncologic diseases of humans. The carcinogen agent N-methyl-N-nitrosourea (MNU) is the oldest member of the nitroso compounds that has the ability to alkylate DNA. MNU is classified as a complete, potent, and direct alkylating compound. Depending on the animals' species and strain, dose, route, and age at the administration, MNU may induce tumors' development in several organs. The aim of this manuscript was to review MNU as a carcinogenic agent, taking into account that this carcinogen agent has been frequently used in experimental protocols to study the carcinogenesis in several tissues, namely breast, ovary, uterus, prostate, liver, spleen, kidney, stomach, small intestine, colon, hematopoietic system, lung, skin, retina, and urinary bladder. In this paper, we also reviewed the experimental conditions to the chemical induction of tumors in different organs with this carcinogen agent, with a special emphasis in the mammary carcinogenesis. PMID:26386719

  3. Carcinogenicity and toxicity of methoxychlor.

    PubMed Central

    Reuber, M D

    1980-01-01

    Methoxychlor is carcinogenic for the liver of C3H and BALB/c mice and Osborne-Mendel rats, and possibly for the liver of dogs. Methoxychlor is also carcinogenic for the testis of BALB/c male mice, bone of B6C3F1 female mice, and the ovary of Osborne-Mendel female rats. The incidences of carcinomas of the liver were increased in C3H male mice and BALB/c male and female mice fed methoxychlor. There also was an increase in malignant neoplasms at all sites in BALB/c male and female mice. C3H and BALB/c male mice were more susceptible to the carcinogenic effects of methoxychlor than were female mice. BALB/c mice were more susceptible than C3H mice. Osborne-Mendel male and female rats developed significant incidences of carcinomas of the liver. The incidence of sarcomas of the spleen and abdomen, mostly hemangiosarcomas, was increased in male rats. Neoplasms of the pituitary, adrenals, and mammary gland were also increased in methoxychlor-treated female rats. Miniature swine given methoxychlor developed chronic renal disease in relatively short periods of time. There also was hyperplasia of the mammary gland and uterus, suggesting an estrogen-like effect on those organs. Methoxychlor applied to the skin of rabbits caused a dose-related atrophy of the testes, as well as chronic renal disease. Atrophy of the testes and chronic renal disease could not be evaluated in mice and rats because of insufficient data. PMID:7000513

  4. [Mutagenic Activity of Four Aminoazo Compounds with Different Carcinogenicity for Rat Liver in the Ames Test].

    PubMed

    Frolova, T S; Sinitsyna, O I; Kaledin, V I

    2015-01-01

    In this paper in the bacterial Ames test we compared the mutagenicity of four aminoazo compounds, previously studied by other researchers and used for activation of rat liver enzymes, with the carcinogenicity in the rat liver. It was found that in the Ames test they have mutagenic activity, however, this activity does not correlate quantitatively with rat sensitivity to their hepatocarcinogenic action. Thus, the most active carcinogen 3'-methyl-4-dimethylaminoazobenzene causes mutations almost 2.5 times less than weakly carcinogenic ortho-aminoazotoluene, and exactly the same number of mutations as non-carcinogenic N,N-diethyl-4-aminoazobenzene. PMID:26591610

  5. Prediction of rodent carcinogenicity for 30 chemicals

    SciTech Connect

    Ashby, J.

    1996-10-01

    Predictions of carcinogenic activity are made for 30 chemicals currently being assessed for rodent carcinogenicity by the U.S. National Toxicology Program. The predictions are based upon the chemical structure, the anticipated or reported mutagenicity, and the reported sub-chronic toxicity of each chemical. It is predicted that 13 chemicals will be noncarcinogenic to rodents, that 7 will be genotoxic carcinogens, and that 10 may show some evidence of presumed nongenotoxic rodent carcinogenesis. 3 refs., 1 fig.

  6. Trichloroethylene. I. Carcinogenicity of trichloroethylene.

    PubMed

    Motohashi, N; Nagashima, H; Molnár, J

    1999-01-01

    Trichloroethylene (TCE) as an industrial pollutant may damage human health and can be considered as carcinogen. TCE has been detected in the environment and in various human organs, e.g., liver, kidney and brain etc. There are histological alterations such as depletion of glycogen and hydropic degeneration in the liver, however, other signs of TCE effects can be found in various organs as well. TCE and its metabolites, e.g., trichlorethanol, trichloro-acetic acid and epoxides were recently identified as strong mutagens in Ames mutagenicity test inducing frameshift and base-substitution mutations. TCE induced predominantly hepatocellular carcinoma after long term administration in mice. In these animals, kidneys and liver were supposed to be primary target organs with low epoxy-hydrolase activity. A high level of mitotic gene conversion (or gene rearrangement) was indicated by the metabolism of TCE after repeated administration. Purified TCE by was a weak mutagen in the presence of S9 microsomal fraction of rats and as a consequence, the carcinogenic activity was low in the kidney of rats. However, a dose related increase of Leydig cell tumors was found in male rats. PMID:10459493

  7. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF BERYLLIUM, BERYLLIUM CHLORIDE, BERYLLIUM FLUORIDE, AND BERYLLIUM NITRATE

    EPA Science Inventory

    Beryllium is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential arcinogenicity from animal studies is "Sufficient," and the evidence from human studies is "Inadequa...

  8. A call to expand regulation to all carcinogenic fibrous minerals

    NASA Astrophysics Data System (ADS)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  9. Induction of hepatocellular carcinoma in nonhuman primates by chemical carcinogens

    SciTech Connect

    Adamson, R.H. )

    1989-01-01

    Several compounds were evaluated in nonhuman primates for their potential to induce neoplasms, especially hepatocellular carcinoma (HCC). The compounds can be classified into three groups: food contaminants, model rodent carcinogens, and nitrosamines. All three compounds in the food contaminants group, namely, aflatoxin B1, sterigmatocystin, and methylazoxymethanol acetate, induced HCC. None of the model rodent carcinogens tested consistently induced HCC in rhesus and cynomolgus monkeys. Three of four nitrosamines evaluated induced HCC in rhesus and cynomolgus monkeys. One nitrosamine, diethylnitrosamine, is a predictable and potent inducer of HCC and is useful for establishment of a nonhuman primate model for numerous oncologic studies.

  10. CARCINOGENIC POTENTIAL OF ROTENONE. PHASE I: DIETARY ADMINISTRATION TO HAMSTERS

    EPA Science Inventory

    Studies were performed to evaluate the potential carcinogenicity rotenone in the Syrian Golden hamster. Several ancillary range-finding studies were carried out including 14-day feeding trials and a reproduction experiment. The latter experiment indicated that rotenone at a level...

  11. Carcinogenic effects of polychlorinated biphenyls.

    PubMed

    Faroon, O M; Keith, S; Jones, D; De Rosa, C

    2001-03-01

    As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites that have the greatest public health impact. These profiles comprehensively summarize toxicological and environmental information. This article constitutes the release of an important section of the Toxicological profile for polychlorinated biphenyls [ATSDR. 2000: Toxicological profile for polychlorinated biphenyls. Atlanta, GA: US Department of Health and Human Services, Agency for Toxic Substances and Disease Registry.] into the scientific literature. This article focuses on the carcinogenic effects of this group of synthetic organic chemicals (polychlorinated biphenyls) in humans and animals. Information on other health effects, toxicokinetics, mechanisms of toxicity, biomarkers, interactions, chemical and physical properties, potential for human exposure, and regulations and advisories is detailed in the profile. PMID:12117297

  12. Health effects of coal mining and combustion: carcinogens and cofactors.

    PubMed Central

    Falk, H L; Jurgelski, W

    1979-01-01

    Some polynuclear aromatics (PNA) have been found to be potent carcinogens for all tissues and organs of experimental animals that have been exposed to them, but different dose levels are needed for these effects. They have been known for decades to cause cancer at the site of application but also at certain sites distant from the area of contact. Although some hydrocarbons are potent and complete carcinogens, the majority of related hydrocarbons was originally found to be inactive. Since they generally appear together, it was important to know more about their interaction, particularly whether they would synergize, or antagonize. The polycyclic hydrocarbons have been studied by subcutaneous injection, where they prove very potent carcinogens. They are also very active on the skin of mice where they produce cancer on prolonged application. Inhalation studies, require larger doses yielded negative results until particulate matter was introduced which facilitated the development of lung tumors. Although iron oxide dust was used initially, other dusts were also capable of enhancing the response of the tissue to benzo(a)pyrene carcinogenesis. This point is of importance, particularly since the inhalation of PNA in situations of air pollution or coal mining involves particulates, although of a different type. Soot is not a homogenous substance and several factors determine its properties. Soots will lose some of the absorbed chemicals during their residence in air, but they retain their PNAs for long periods of time when they reach the soil. The carcinogenicity of PNAs in the adsorbed state may be completely absent, depending on particle size of the soot and availability of eluting capability of the tissues or cells in contact with the soot. Whenever the carcinogenic polynuclear aromatics can be eluted they will be active in producing cancer if their residence is adequate. There seems to be no reason to assume that a large increase in coal combustion in the future will

  13. PROPOSED GUIDELINES FOR CARCINOGEN RISK ASSESSMENT

    EPA Science Inventory

    The Proposed Guidelines for Carcinogen Risk Assessment were published in the Federal Register on April 23, 1996 (Federal Register: 17960-18011) for a 120-day public review and comment period. The Proposed Guidelines are a revision of EPA's 1986 Guidelines for Carcinogen Risk Ass...

  14. FACTORS INFLUENCING AGE AND STRAIN-RELATED SUSCEPTIBILITY TO 3-METHYLCHOLANTHRENE CARCINOGENICITY

    EPA Science Inventory

    Fetal mice are more sensitive to chemical carcinogens than are adults. Further, some strains of mice are more susceptible to chemical carcinogens than others. We have been conducting studies to understand the interactions between age and genetic background underlying these suscep...

  15. JaCVAM-organized international validation study of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: I. Summary of pre-validation study results.

    PubMed

    Uno, Yoshifumi; Kojima, Hajime; Omori, Takashi; Corvi, Raffaella; Honma, Masamistu; Schechtman, Leonard M; Tice, Raymond R; Burlinson, Brian; Escobar, Patricia A; Kraynak, Andrew R; Nakagawa, Yuzuki; Nakajima, Madoka; Pant, Kamala; Asano, Norihide; Lovell, David; Morita, Takeshi; Ohno, Yasuo; Hayashi, Makoto

    2015-07-01

    The in vivo rodent alkaline comet assay (comet assay) is used internationally to investigate the in vivo genotoxic potential of test chemicals. This assay, however, has not previously been formally validated. The Japanese Center for the Validation of Alternative Methods (JaCVAM), with the cooperation of the U.S. NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)/the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the European Centre for the Validation of Alternative Methods (ECVAM), and the Japanese Environmental Mutagen Society/Mammalian Mutagenesis Study Group (JEMS/MMS), organized an international validation study to evaluate the reliability and relevance of the assay for identifying genotoxic carcinogens, using liver and stomach as target organs. The ultimate goal of this validation effort was to establish an Organisation for Economic Co-operation and Development (OECD) test guideline. The purpose of the pre-validation studies (i.e., Phase 1 through 3), conducted in four or five laboratories with extensive comet assay experience, was to optimize the protocol to be used during the definitive validation study. PMID:26212293

  16. A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study.

    PubMed

    Swart, Karin M A; Ham, Annelies C; van Wijngaarden, Janneke P; Enneman, Anke W; van Dijk, Suzanne C; Sohl, Evelien; Brouwer-Brolsma, Elske M; van der Zwaluw, Nikita L; Zillikens, M Carola; Dhonukshe-Rutten, Rosalie A M; van der Velde, Nathalie; Brug, Johannes; Uitterlinden, André G; de Groot, Lisette C P G M; Lips, Paul; van Schoor, Natasja M

    2016-01-01

    Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95% CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95% CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies. PMID:26412463

  17. COMPLEMENTARITY OF GENOTOXIC AND NONGENOTOXIC PREDICTORS OF RODENT CARCINOGENICITY

    EPA Science Inventory

    Twenty-one chemicals known to be carcinogenic in rodent bioassays were selected for study. he chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. he effects of these 21 chemicals on four biochemical assays (hepatic DNA damage by alkaline elutio...

  18. POTENTIAL ATMOSPHERIC CARCINOGENS, PHASE 1. IDENTIFICATION AND CLASSIFICATION

    EPA Science Inventory

    A comprehensive literature search identified more than 125 high-volume chemicals having the potential of becoming airborne carcinogenic pollutants. Based on carcinogenicity and mutagenicity data, the pollutants were divided into three categories: probable carcinogens, possible ca...

  19. Dichlorvos carcinogenicity: an assessment of the weight of experimental evidence.

    PubMed

    Mennear, J H

    1994-12-01

    After 30 years of experience with human exposure to dichlorvos (DDVP) in the home, workplace, and sickroom, the U.S. EPA has published its intent to revoke the food additive registration of this cholinesterase-inhibiting insecticide. The basis for the Agency action is the result of the National Toxicology Program (NTP) toxicology and carcinogenesis study of DDVP in rats and mice (NTP Technical Report No. 342, September 1989). In those experiments the NTP considered the result in the female mouse portion of the study to afford unequivocal evidence of carcinogenicity. The NTP considered the interpretations of the male and female rat and the male mouse studies to be less than clear. Despite the NTP interpretation, the EPA considers the male rat data (increased incidence of mononuclear cell leukemia) to be sufficient to warrant the regulatory change. The purpose of this report is to summarize a review of the interpretation of the NTP data and to assess the predictive validity of the results relative to potential human health impact. Critical review of experimental data indicates that the evidence for a carcinogenic effect of DDVP in animals is equivocal. Further, DDVP possess no in vivo mutagenic activity in mammalian assay systems and it bears no significant structural similarity to known carcinogens. Therefore, a weight-of-the-evidence analysis leads to the conclusion that DDVP poses neither mutagenic nor carcinogenic risks to humans exposed under normal conditions of use of foreseeable conditions of misuse. PMID:7724838

  20. Results of the International Validation of the in vivo rodent alkaline comet assay for the detection of genotoxic carcinogens: Individual data for 1,2-dibromoethane, p-anisidine, and o-anthranilic acid in the 2nd step of the 4th phase Validation Study under the JaCVAM initiative.

    PubMed

    Takasawa, Hironao; Takashima, Rie; Narumi, Kazunori; Kawasako, Kazufumi; Hattori, Akiko; Kawabata, Masayoshi; Hamada, Shuichi

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative International Validation Study of an in vivo rat alkaline comet assay, we examined 1,2-dibromoethane (DBE), p-anisidine (ASD), and o-anthranilic acid (ANT) to investigate the effectiveness of the comet assay in detecting genotoxic carcinogens. Each of the three test chemicals was administered to 5 male Sprague-Dawley rats per group by oral gavage at 48, 24, and 3h before specimen preparation. Single cells were collected from the liver and glandular stomach at 3h after the final dosing, and the specimens prepared from these two organs were subjected to electrophoresis under alkaline conditions (pH>13). The percentage of DNA intensity in the comet tail was then assessed using an image analysis system. A micronucleus (MN) assay was also conducted using these three test chemicals with the bone marrow (BM) cells collected from the same animals simultaneously used in the comet assay, i.e., combination study of the comet assay and BM MN assay. A genotoxic (Ames positive) rodent carcinogen, DBE gave a positive result in the comet assay in the present study, while a genotoxic (Ames positive) non-carcinogen, ASD and a non-genotoxic (Ames negative) non-carcinogen, ANT showed negative results in the comet assay. All three chemicals produced negative results in the BM MN assay. While the comet assay findings in the present study were consistent with those obtained from the rodent carcinogenicity studies for the three test chemicals, we consider the positive result in the comet assay for DBE to be particularly meaningful, given that this chemical produced a negative result in the BM MN assay. Therefore, the combination study of the comet assay and BM MN assay is a useful method to detect genotoxic carcinogens that are undetectable with the BM MN assay alone. PMID:26212305

  1. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    PubMed

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample. PMID:21524677

  2. Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

    PubMed

    Brown, R C; Davis, J M; Douglas, D; Gruber, U F; Hoskins, J A; Ilgren, E B; Johnson, N F; Rossiter, C E; Wagner, J C

    1991-08-01

    In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans. PMID:1947241

  3. Computer-Guided Implant Surgery in Fresh Extraction Sockets and Immediate Loading of a Full Arch Restoration: A 2-Year Follow-Up Study of 14 Consecutively Treated Patients.

    PubMed

    Daas, M; Assaf, A; Dada, K; Makzoumé, J

    2015-01-01

    Statement of Problem. Low scientific evidence is identified in the literature for combining implant placement in fresh extraction sockets with immediate function. Moreover, the few studies available on immediate implants in postextraction sites supporting immediate full-arch rehabilitation clearly lack comprehensive protocols. Purpose. The purpose of this study is to report outcomes of a comprehensive protocol using CAD-CAM technology for surgical planning and fabrication of a surgical template and to demonstrate that immediate function can be easily performed with immediate implants in postextraction sites supporting full-arch rehabilitation. Material and Methods. 14 subjects were consecutively rehabilitated (13 maxillae and 1 mandible) with 99 implants supporting full-arch fixed prostheses followed between 6 and 24 months (mean of 16 months). Outcome measures were prosthesis and implant success, biologic and prosthetic complications, pain, oedema evaluation, and radiographic marginal bone levels at surgery and then at 6, 12, 18, and 24 months. Data were analyzed with descriptive statistics. Results. The overall cumulative implant survival rate at mean follow-up time of 16 months was 97.97%. The average marginal bone loss was 0,9 mm. Conclusions. Within the limitations of this study, the results validate this treatment modality for full-arch rehabilitations with predictable outcomes and high survival rate after 2 years. PMID:26064119

  4. Computer-Guided Implant Surgery in Fresh Extraction Sockets and Immediate Loading of a Full Arch Restoration: A 2-Year Follow-Up Study of 14 Consecutively Treated Patients

    PubMed Central

    Daas, M.; Assaf, A.; Dada, K.; Makzoumé, J.

    2015-01-01

    Statement of Problem. Low scientific evidence is identified in the literature for combining implant placement in fresh extraction sockets with immediate function. Moreover, the few studies available on immediate implants in postextraction sites supporting immediate full-arch rehabilitation clearly lack comprehensive protocols. Purpose. The purpose of this study is to report outcomes of a comprehensive protocol using CAD-CAM technology for surgical planning and fabrication of a surgical template and to demonstrate that immediate function can be easily performed with immediate implants in postextraction sites supporting full-arch rehabilitation. Material and Methods. 14 subjects were consecutively rehabilitated (13 maxillae and 1 mandible) with 99 implants supporting full-arch fixed prostheses followed between 6 and 24 months (mean of 16 months). Outcome measures were prosthesis and implant success, biologic and prosthetic complications, pain, oedema evaluation, and radiographic marginal bone levels at surgery and then at 6, 12, 18, and 24 months. Data were analyzed with descriptive statistics. Results. The overall cumulative implant survival rate at mean follow-up time of 16 months was 97.97%. The average marginal bone loss was 0,9 mm. Conclusions. Within the limitations of this study, the results validate this treatment modality for full-arch rehabilitations with predictable outcomes and high survival rate after 2 years. PMID:26064119

  5. Detection of rare and possibly carcinogenic human papillomavirus genotypes as single infections in invasive cervical cancer.

    PubMed

    Geraets, Daan; Alemany, Laia; Guimera, Nuria; de Sanjose, Silvia; de Koning, Maurits; Molijn, Anco; Jenkins, David; Bosch, Xavier; Quint, Wim

    2012-12-01

    The contribution of carcinogenic human papillomavirus (HPV) types to the burden of cervical cancer has been well established. However, the role and contribution of phylogenetically related HPV genotypes and rare variants remains uncertain. In a recent global study of 8977 HPV-positive invasive cervical carcinomas (ICCs), the genotype remained unidentified in 3.7% by the HPV SPF10 PCR-DEIA-LiPA25 (version 1) algorithm. The 331 ICC specimens with unknown genotype were analysed by a novel sequence methodology, using multiple selected short regions in L1. This demonstrated HPV genotypes that have infrequently or never been detected in ICC, ie HPV26, 30, 61, 67, 68, 69, 73 and 82, and rare variants of HPV16, 18, 26, 30, 34, 39, 56, 67, 68, 69, 82 and 91. These are not identified individually by LiPA25 and only to some extent by other HPV genotyping assays. Most identified genotypes have a close phylogenetic relationship with established carcinogenic HPVs and have been classified as possibly carcinogenic by IARC. Except for HPV85, all genotypes in α-species 5, 6, 7, 9 and 11 were encountered as single infections in ICCs. These species of established and possibly carcinogenic HPV types form an evolutionary clade. We have shown that the possibly carcinogenic types were detected only in squamous cell carcinomas, which were often keratinizing and diagnosed at a relatively higher mean age (55.3 years) than those associated with established carcinogenic types (50.9 years). The individual frequency of the possibly carcinogenic types in ICCs is low, but together they are associated with 2.25% of the 8338 included ICCs with a single HPV type. This fraction is greater than seven of the established carcinogenic types individually. This study provides evidence that possibly carcinogenic HPV types occur as single infections in invasive cervical cancer, strengthening the circumstantial evidence of a carcinogenic role. PMID:22711526

  6. Carcinogenicity and epidemiological profile analysis of vinyl chloride and polyvinyl chloride

    SciTech Connect

    Kalmaz, E.E.; Kalmaz, G.D.

    1984-03-01

    The carcinogenicity of vinyl chloride and polyvinyl chloride (VC/PVC) is reviewed with specific attention to the gaps in knowledge for risk estimation and epidemiological presentation of the available data. Although experimental studies have demonstrated the carcinogenicity and mutagenicity of VC/PVC in general, the epidemiologic studies available for review do not include an assessment of carcinogenic risk among humans exposed to these chemicals. This conclusion is based on the observation that the majority of cohort studies reviewed lacked sufficient statistical power because of small sample sizes. Further, in epidemiological studies, individuals were not followed over an adequate period of time during which cancer could become clinically manifest.

  7. Structure-activity studies of the carcinogenicities in the mouse and rat of some naturally occurring and synthetic alkenylbenzene derivatives related to safrole and estragole.

    PubMed

    Miller, E C; Swanson, A B; Phillips, D H; Fletcher, T L; Liem, A; Miller, J A

    1983-03-01

    Twenty-three naturally occurring and synthetic alkenylbenzene derivatives structurally related to the hepatocarcinogen safrole (1-allyl-3,4-methylenedioxybenzene) were assayed for their hepatocarcinogenicity in mice. Some of these compounds (safrole, estragole, eugenol, anethole, methyleugenol, myristicin, elemicin, and dill and parsley apiols) may be ingested in very small amounts by human as natural components of certain spices, essential oils, or vegetables. Estragole (1-allyl-4-methoxybenzene) and its proximate carcinogenic metabolite 1'-hydroxyestragole, previously shown to induce hepatic tumors when administered to male CD-1 mice only during the preweaning period, also induced hepatic tumors on administration for 12 months in the diet of female CD-1 mice. Eugenol (1-allyl-4-hydroxy-3-methoxybenzene) and anethole (trans-4-methoxy-1-propenylbenzene) were inactive in this assay; they were also inactive when administered i.p. during the preweaning period at total doses of up to 9.45 mumol/mouse to male CD-1 or C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. Methyleugenol (1-ally-3,4-dimethoxybenzene) and its 1'-hydroxy metabolite had activities similar to those of estragole and its 1'-hydroxy metabolite for the induction of hepatic tumors in male B6C3F1 mice treated prior to weaning; 1-allyl-1'-hydroxy-4-methoxynaphthalene was somewhat less active. At the levels tested, myristicin (1-allyl-5-methoxy-3,4-methylenedioxybenzene), elemicin (1-allyl-3,4,5-trimethoxybenzene) and its 1'-hydroxy metabolite, dill apiol (1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene), parsley apiol (1-allyl-2,5-dimethoxy-3,4-methylenedioxybenzene), 1'-hydroxyallybenzene, 3'-hydroxyanethole, and benzyl and anisyl alcohols had no detectable activity for the initiation of hepatic tumors on administration to male mice prior to weaning. The acetylenic derivative 1'-hydroxy-2',3'-dehydroestragole was much more active than either 1'-hydroxysafrole or 1'-hydroxyestragole when administered to

  8. Triadic Interaction among Newly Acquainted 2-Year-Olds

    ERIC Educational Resources Information Center

    Ishikawa, Fumiko; Hay, Dale F.

    2006-01-01

    Are children as young as 2 years old able to interact in groups of three? The study applied the family triad model first introduced by Parke, Power, and Gottman (1979) to the case of peer interaction. In Experiment 1, the model was refined for use in studies of peer interaction and applied to an existing dataset of 16 triads of newly acquainted…

  9. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the k sub e test

    SciTech Connect

    Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

    1989-01-01

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs.

  10. Decrease in self-esteem mediates the association between symptoms of social phobia and depression in middle adolescence in a sex-specific manner: a 2-year follow-up of a prospective population cohort study

    PubMed Central

    2014-01-01

    Background Social phobia and depression are common, highly comorbid disorders in middle adolescence. The mechanism underlying this comorbidity, however, is unclear. Decrease in self-esteem caused by the initial disorder might play a decisive role in the development of the subsequent disorder. The present study aimed to determine whether the association between symptoms of social phobia and depression is mediated by decrease in self-esteem in mid-adolescent girls and boys. Methods As a part of the prospective Adolescent Mental Health Cohort (AMCH), subjects of this study were 9th grade pupils (mean age, 15.5) responding to a survey conducted in 2002–2003 (T1) and to a 2-year follow-up survey in 2004–2005 (T2) (N = 2070, mean age 17.6 years, 54.5% girls). Results Symptoms of social phobia without symptoms of depression at age 15 and symptoms of depression at age 17 were associated only among boys, and this association was mediated by decrease in self-esteem. Symptoms of depression without symptoms of social phobia at age 15 and symptoms of social phobia at age 17 were associated only among girls, and this association was partially mediated by decrease in self-esteem. Conclusions Decrease in self-esteem plays a decisive role in the association between social phobia and depression. Self-esteem should be a key focus in interventions for adolescents suffering from social phobia or depression. Efficient intervention for the first disorder might help to prevent the decline in self-esteem and thus the incidence of the subsequent disorder. These findings are based on a sample of Finnish adolescents and should be confirmed in other jurisdictions or in more ethnically diverse samples. PMID:24641987

  11. Association between inflammatory cytokines and the risk of post-stroke depression, and the effect of depression on outcomes of patients with ischemic stroke in a 2-year prospective study

    PubMed Central

    Jiao, Jian-Tong; Cheng, Chao; Ma, Ying-Jun; Huang, Jin; Dai, Min-Chao; Jiang, Chen; Wang, Cheng; Shao, Jun-Fei

    2016-01-01

    The association between inflammatory cytokines and the risk of post-stroke depression (PSD) remains unclear. The aim of the present study was to investigate this association and the effect of PSD on the outcomes of ischemic stroke patients. A total of 355 patients who had experienced ischemic stroke participated in inflammatory cytokine detection by ELISA, in addition to depression, quality of life (QOL) and body performance testing. Cox regression was used to evaluate the associations between PSD risk, inflammatory cytokines and the outcomes of patients. Measurement data was evaluated using Student's t test, and counted data was measured by χ2 test. The incidence of PSD during the 2-year follow-up was 23.1%. The risk of PSD elevated with increased interleukin (IL)-6 expression levels [hazard ratio (HR)=3.18; 95% confidence interval (CI), 1.37–7.36] following the adjustment of confounders. However, no significant associations were identified between PSD and other inflammatory cytokines. QOL and body performance in the depressed group were significantly worse compared with those in the non-depressed group. The risk of stroke recurrence in patients with depression increased two-fold compared with patients without depression (HR=2.020; 95% CI, 1.123–3.635; Ptrend=0.019). No significant associations between PSD and the risk of mortality (HR=1.497; 95% CI, 0.547–4.098) were observed. In conclusion, depression is prevalent in patients following ischemic stroke. IL-6 is positively associated with the risk of PSD, and may predict its development in patients following ischemic stroke. PSD correlates with outcomes of patients, and the effective management of PSD may improve the prognosis of patients. PMID:27588080

  12. French multicenter phase III randomized study testing concurrent twice-a-day radiotherapy and cisplatin/5-fluorouracil chemotherapy (BiRCF) in unresectable pharyngeal carcinoma: Results at 2 years (FNCLCC-GORTEC)

    SciTech Connect

    Bensadoun, Rene-Jean . E-mail: rene-jean.bensadoun@nice.fnclcc.fr; Benezery, Karen; Dassonville, Olivier; Magne, Nicolas; Poissonnet, Gilles; Ramaioli, Alain; Lemanski, Claire; Bourdin, Sylvain; Tortochaux, Jacques; Peyrade, Frederic; Marcy, Pierre-Yves; Chamorey, Emmanuel Phar; Vallicioni, Jacques; Seng Hang; Alzieu, Claude; Gery, Bernard; Chauvel, Pierre; Schneider, Maurice; Santini, Jose; Demard, Francois; Calais, Gilles

    2006-03-15

    Background: Unresectable carcinomas of the oropharynx and hypopharynx still have a poor long-term prognosis. Following a previous phase II study, this phase III multicenter trial was conducted between November 1997 and March 2002. Methods: Nontreated, strictly unresectable cases were eligible. Twice-daily radiation: two fractions of 1.2 Gy/day, 5 days per week, with no split (D1{sup {yields}}D46). Total tumor doses: 80.4 Gy/46 day (oropharynx), 75.6 Gy/44 day (hypopharynx). Chemotherapy (arm B): Cisplatin 100 mg/m{sup 2} (D1, D22, D43); 5FU, continuous infusion (D1{sup {yields}}D5), 750 mg/m{sup 2}/day cycle 1; 430 mg/m{sup 2}/day cycles 2 and 3. Results: A total of 163 evaluable patients. Grade 3-4 acute mucositis 82.6% arm B/69.5% arm A (NS); Grade 3-4 neutropenia 33.3% arm B/2.4% arm A (p < 0.05). Enteral nutrition through gastrostomy tube was more frequent in arm B before treatment and at 6 months (p < 0.01). At 24 months, overall survival (OS), disease-free survival (DFS), and specific survival (SS) were significantly better in arm B. OS: 37.8% arm B vs. 20.1% arm A (p = 0.038); DFS: 48.2% vs. 25.2% (p = 0.002); SS: 44.5% vs. 30.2% (p 0.021). No significant difference between the two arms in the amount of side effects at 1 and 2 years. Conclusion: For these unresectable cases, chemoradiation provides better outcome than radiation alone, even with an 'aggressive' dose-intensity radiotherapy schedule.

  13. Variation in the effect of five chemical carcinogens on the plaque-forming cell response

    SciTech Connect

    Raikow, R.B.; OKunewick, J.P.; Buffo, M.J.; Jones, D.L.

    1983-03-01

    The effect of five different chemical carcinogens on plaque-forming cell response was measured in order to obtain an index of their effect on humoral antibody formation in vivo. Two alkyl sulfonates: methyl methane sulfonate (MMS) and 1,3-propane sultone (PS); along with three polycyclic aromatic hydrocarbons: benzo(a)pyrene (BP); 7,12-dimethyl benzanthracene (DMBA); and 20-methylcholanthrene (MCA) were chosen for these studies. Each carcinogen was administered as a single intraperitoneal injection to SJL/J mice, and the ability of the animals to generate plaque forming cells to sheep red blood cell antigens was measured as a function of time after exposure to the carcinogen. Some suppression of this humoral immune response was observed with all of the carcinogens tested. The amount and duration of this suppression varied as a function of both the type of carcinogen and the dose. Of the five carcinogens tested only DMBA and MCA produced an immunosuppressive effect that might correlate with their reported carcinogenicity, and PS administration actually resulted in a brief immunostimulatory response during the first four days after administration.

  14. Applying Tobacco Carcinogen and Toxicant Biomarkers in Product Regulation and Cancer Prevention

    PubMed Central

    Hecht, Stephen S.; Yuan, Jian-Min; Hatsukami, Dorothy

    2010-01-01

    Tobacco carcinogen and toxicant biomarkers are metabolites or protein or DNA adducts of specific compounds in tobacco products. Highly reliable analytical methods, based mainly on mass spectrometry, have been developed and applied in large studies of many of these biomarkers. A panel of tobacco carcinogen and toxicant biomarkers is suggested here, and typical values for smokers and non-smokers are summarized. This panel of biomarkers has potential applications in the new and challenging area of tobacco product regulation and in development of rational approaches to cancer prevention by establishing carcinogen and toxicant uptake and excretion in people exposed to tobacco products. PMID:20408564

  15. EVALUATION OF MUTAGENIC AND CARCINOGENIC PROPERTIES OF BROMINATED AND CHLORINATED ACETONITRILES: BY-PRODUCTS OF CHLORINATION

    EPA Science Inventory

    The present study was undertaken to determine if chlorinated and brominated acetonitriles formed during the chlorination of drinking water possess mutagenic and/or carcinogenic properties. Chloroacetonitrile (CAN), dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN), bromoc...

  16. INTERACTION BETWEEN NORMAL HUMAN DIPLOID CELLS AND CHEMICAL CARCINOGENS/MUTAGENS 'IN VITRO'

    EPA Science Inventory

    The objectives of the present studies were to develop sensitive, reproducible methods for detecting mutations in normal human fibroblast cells and to demonstrate dose-related mutagenesis by known and potential carcinogens. The authors have modified conventional test procedures fo...

  17. The multitude and diversity of environmental carcinogens

    SciTech Connect

    Belpomme, D. Irigaray, P.; Hardell, L.; Clapp, R.; Montagnier, L.; Epstein, S.; Sasco, A.J.

    2007-11-15

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment.

  18. A minimum 2-year comparative study of autologous cancellous bone grafting versus beta-tricalcium phosphate in anterior cervical discectomy and fusion using a rectangular titanium stand-alone cage.

    PubMed

    Yamagata, Toru; Naito, Kentaro; Arima, Hironori; Yoshimura, Masaki; Ohata, Kenji; Takami, Toshihiro

    2016-07-01

    Although titanium stand-alone cages are commonly used in anterior cervical discectomy and fusion (ACDF), there are several concerns such as cage subsidence after surgery. The efficacy of β-tricalcium phosphate (β-TCP) granules as a packing material in 1- or 2-level ACDF using a rectangular titanium stand-alone cage is not fully understood. The purpose of this study is to investigate the validity of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP. This retrospective study included 55 consecutive patients who underwent ACDF with autologous iliac cancellous bone grafting and 45 consecutive patients with β-TCP grafting. All patients completed at least 2-year postoperative follow-up. Univariate and multivariate analyses were performed to examine the associations between study variables and nonunion after surgery. Significant neurological recovery after surgery was obtained in both groups. Cage subsidence was noted in 14 of 72 cages (19.4 %) in the autograft group and 12 of 64 cages (18.8 %) in the β-TCP group. A total of 66 cages (91.7 %) in the autograft group showed osseous or partial union, and 58 cages (90.6 %) in the β-TCP group showed osseous or partial union by 2 years after surgery. There were no significant differences in cage subsidence and the bony fusion rate between the two groups. Multivariate analysis using a logistic regression model showed that fusion level at C6/7, 2-level fusion, and cage subsidence of grades 2-3 were significantly associated with nonunion at 2 years after surgery. Although an acceptable surgical outcome with negligible complication appears to justify the use of rectangular titanium stand-alone cages in 1- and 2-level ACDF with β-TCP, cage subsidence after surgery needs to be avoided to achieve acceptable bony fusion at the fused segments. Fusion level at C6/7 or 2-level fusion may be another risk factor of nonunion. PMID:27098659

  19. Application of the improved BALB/c 3T3 cell transformation assay to the examination of the initiating and promoting activities of chemicals: the second interlaboratory collaborative study by the non-genotoxic carcinogen study group of Japan.

    PubMed

    Tsuchiya, Toshiyuki; Umeda, Makoto; Tanaka, Noriho; Sakai, Ayako; Nishiyama, Hiroshi; Yoshimura, Isao; Ajimi, Syozo; Asada, Shin; Asakura, Masumi; Baba, Hiroshi; Dewa, Yasuaki; Ebe, Youji; Fushiwaki, Yuichi; Hagiwara, Yuji; Hamada, Shuichi; Hamamura, Tetsuo; Iwase, Yumiko; Kajiwara, Yoshitsugu; Kasahara, Yasushi; Kato, Yukihiko; Kawabata, Masayoshi; Kitada, Emiko; Kaneko, Kazuko; Kizaki, Yuko; Kubo, Kinya; Miura, Daisaku; Mashiko, Kaori; Mizuhashi, Fukutaro; Muramatsu, Dai; Nakajima, Madoka; Nakamura, Tetsu; Oishi, Hidetoshi; Sasaki, Toshiaki; Shimada, Sawako; Takahashi, Chitose; Takeda, Yuko; Wakuri, Sinobu; Yajima, Nobuhiro; Yajima, Satoshi; Yatsushiro, Tomoko

    2010-03-01

    The Non-genotoxic Carcinogen Study Group in the Environmental Mutagen Society of Japan organised the second step of the inter-laboratory collaborative study on one-stage and two-stage cell transformation assays employing BALB/c 3T3 cells, with the objective of confirming whether the respective laboratories could independently produce results relevant to initiation or promotion. The method was modified to use a medium consisting of DMEM/F12 supplemented with 2% fetal bovine serum and a mixture of insulin, transferrin, ethanolamine and sodium selenite, at the stationary phase of cell growth. Seventeen laboratories collaborated in this study, and each chemical was tested by three to five laboratories. Comparison between the one-stage and two-stage assays revealed that the latter method would be beneficial in the screening of chemicals. In the test for initiating activity with the two-stage assay (post-treated with 0.1microg/ml 12-O-tetradecanoylphorbol-13-acetate), the relevant test laboratories all obtained positive results for benzo[a]pyrene and methylmethane sulphonate, and negative results for phenanthrene. Of those laboratories assigned phenacetin for the initiation phase, two returned positive results and two returned negative results, where the latter laboratories tested up to one dose lower than the maximum dose used by the former laboratories. In the exploration of promoting activity with the twostage assay (pretreated with 0.2microg/ml 3-methylcholanthrene), the relevant test laboratories obtained positive results for mezerein, sodium orthovanadate and TGF-beta1, and negative results for anthralin, phenacetin and phorbol. Two results returned for phorbol 12,13-didecanoate were positive, but one result was negative - again, the maximum dose to achieve the latter result was lower than that which produced the former results. These results suggest that this modified assay method is relevant, reproducible and transferable, provided that dosing issues, such as the

  20. Genotoxicity and carcinogenicity of acrylamide: a critical review.

    PubMed

    Carere, Angelo

    2006-01-01

    In 2002, public health concerns were raised by Swedish studies showing that relatively high levels of acrylamide were formed during the frying, roasting, or baking of a variety of foods, including potatoes, cereal products and coffee at temperatures above 120 degrees C. Acrylamide possesses a range of hazardous properties, the key effects being carcinogenicity, genotoxicity, neurotoxicity and reproductive toxicity. Acrylamide is clearly carcinogenic in studies in animals, in which it causes increased tumour incidence at a variety of sites. Although the mechanisms for tumour induction in experimental animals have not yet fully elucidated, the in vivo genotoxicity at gene and chromosome level in somatic and germ cells in rodents cannot be discounted from contributing to it. At this time, there is no information to indicate any significant difference between rodents and humans in sensitivity to cancer formation from acrylamide. The present available epidemiological studies of human industrial and accidental exposures have to be considered not suitable for use in the cancer risk assessment of acrylamide in food, due to several limitations. In reviewing the genotoxicity and carcinogenicity of acrylamide, the author has taken into account also the evaluations made by the IARC in 1994, the FAO/WHO in 2002 by the European Commission Scientific Committee on Food (SCF) in 2002 and by the Joint FAO/WHO Expert Committee on Food Additive (JECFA) in 2005. PMID:17033134

  1. Artificial sweeteners--do they bear a carcinogenic risk?

    PubMed

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible. PMID:15367404

  2. Contributions of Human Enzymes in Carcinogen Metabolism

    PubMed Central

    Rendic, Slobodan; Guengerich, F. Peter

    2012-01-01

    Considerable support exists for roles of metabolism in modulating the carcinogenic properties of chemicals. In particular, many of these compounds are procarcinogens that require activation to electrophilic forms to exert genotoxic effects. We systematically analyzed the existing literature on metabolism of carcinogens by human enzymes, which has been developed largely in the past 25 years. The metabolism and especially bioactivation of carcinogens are dominated by cytochrome P450 enzymes (66% of bioactivations). Within this group, six P450s—1A1, 1A2, 1B1, 2A6, 2E1, and 3A4—accounted for 77% of the P450 activation reactions. The roles of these P450s can be compared with those estimated for drug metabolism and should be considered in issues involving enzyme induction, chemoprevention, molecular epidemiology, inter-individual variations, and risk assessment. PMID:22531028

  3. The ISS Carcinogens Data Bank (BDC).

    PubMed

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida

    2008-01-01

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant website. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents. PMID:18469374

  4. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    PubMed

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  5. Smoking Patterns, Attitudes and Motives: Unique Characteristics among 2-Year versus 4-Year College Students

    ERIC Educational Resources Information Center

    Berg, C. J.; An, L. C.; Thomas, J. L.; Lust, K. A.; Sanem, J. R.; Swan, D. W.; Ahluwalia, J. S.

    2011-01-01

    Given the previously documented higher rates of smoking among 2-year college students in comparison with 4-year university students, this study compares smoking patterns, attitudes and motives among 2-year and 4-year college students. Two thousand two hundred and sixty-five undergraduate students aged 18-25 years at a 2-year college and a 4-year…

  6. Comparison between carcinogenicity and mutagenicity based on chemicals evaluated in the IARC monographs.

    PubMed Central

    Bartsch, H; Tomatis, L

    1983-01-01

    The qualitative relationship between carcinogenicity and mutagenicity (DNA-damaging activity), based on chemicals which are known to be or suspected of being carcinogenic to man and/or to experimental animals, is analyzed using 532 chemicals evaluated in Volumes 1-25 of the IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. About 40 compounds (industrial processes) were found to be either definitely or probably carcinogenic to man, and 130 chemicals have been adequately tested in rodents and most of them also in various short-term assays. For a comparison between the carcinogenicity of a chemical and its behavior in short-term tests, systems were selected that have a value for predicting carcinogenicity. These were divided into mutagenicity in (A) the S. typhimurium/microsome assay, (B) other submammalian systems and (C) cultured mammalian cells; (D) chromosomal abnormalities in mammalian cells; (E) DNA damage and repair; (F) cell transformation (or altered growth properties) in vitro. The following conclusions can be drawn. In the absence of studies in man, long-term animal tests are still today the only ones capable of providing evidence of the carcinogenic effect of a chemical. The development and application of an appropriate combination of short-term tests (despite current limitations) can significantly contribute to the prediction/confirmation of the carcinogenic effects of chemicals in animals/man. Confidence in positive tests results is increased when they are confirmed in multiple short-term tests using nonrepetitive end points and different activation systems. Assays to detect carcinogens which do not act via electrophiles (promoters) need to be developed. The results of a given short-term test should be interpreted in the context of other toxicological data. Increasing demand for quantitative carcinogenicity data requires further examination of whether or not there is a quantitative relationship between the potency of a

  7. Pulmonary carcinogenicity of inhaled particles and the maximum tolerated dose.

    PubMed Central

    Oberdörster, G

    1997-01-01

    Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. The influence of high experimental doses on tumor development has been recognized for some time and has led to the concept of maximum tolerated dose (MTD) for dose selection, with the highest dose being at the MTD. Exposure at the MTD should ensure that the animals are sufficiently challenged while at the same time the animal's normal longevity is not altered from effects other than carcinogenicity. A characteristic of exposure-dose-response relationships for chronically inhaled particles is that lung tumors are significantly increased only at high exposure levels, and that lung tumors are seen in rats only but not in mice or hamsters. This lung tumor response in rats is thought to be secondary to persistent alveolar inflammation, indicating that the MTD may have been exceeded. Thus, mechanisms of toxicity and carcinogenicity may be dose dependent and may not operate at lower doses that humans normally experience. Despite awareness of this problem, carcinogenicity bioassays that evaluate particulate compounds in rodents have not always been designed with the MTD concept in mind. This is due to several problems associated with determining an appropriate MTD for particle inhalation studies. One requirement for the MTD is that some toxicity should be observed. However, it is difficult to define what degree of toxic response is indicative of the MTD. For particle inhalation studies, various noncancer end points in addition to mortality and body weight gain have been considered as indicators of the MTD, i.e., pulmonary inflammation, increased epithelial cell proliferation, increased lung weight, impairment of particle clearance function, and significant histopathological findings at the end of a subchronic study. However, there is no general agreement about quantification of these end points to define the

  8. Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens.

    PubMed

    Iida, Mari; Anna, Colleen H; Holliday, Wanda M; Collins, Jennifer B; Cunningham, Michael L; Sills, Robert C; Devereux, Theodora R

    2005-03-01

    Previously we demonstrated that the mouse liver tumor response to the non-genotoxic carcinogens oxazepam and Wyeth-14,643 involved more differences than similarities in changes in early gene expression. In this study we used quantitative real-time PCR and oligonucleotide microarray analysis to identify genes that were up- or down-regulated in mouse liver early after treatment with different known carcinogens, including oxazepam (125 and 2500 p.p.m.), o-nitrotoluene (1250 and 5000 p.p.m.) and methyleugenol (75 mg/kg/day), or the non-carcinogens p-nitrotoluene (5000 p.p.m.), eugenol (75 mg/kg/day) and acetaminophen (6000 p.p.m.). Starting at 6 weeks of age, mice were treated with the different compounds for 2 weeks in the diet, at which time the livers were collected. First, expression of 12 genes found previously to be altered in liver after 2 weeks treatment with oxazepam and/or Wyeth-14,643 was examined in livers from the various chemical treatment groups. These gene expression changes were confirmed for the livers from the oxazepam-treated mice in the present study, but were not good early markers for all the carcinogens in this study. In addition, expression of 20 842 genes was assessed by oligonucleotide microarray [n = 4 livers/group, 2 hybridizations/liver (with fluor reversals)] and the results were analyzed using the Rosetta Resolver System and GeneSpring software. The analyses revealed that several cancer-related genes, including Fhit, Wwox, Tsc-22 and Gadd45b, were induced or repressed in unique patterns for specific carcinogens and not altered by the non-carcinogens. The data indicate that even if the tumor response, including molecular alterations, is similar, such as for oxazepam and methyleugenol, early gene expression changes appear to be carcinogen specific and seem to involve apoptosis and cell cycle-related genes. PMID:15618236

  9. (35S)methionine interaction with rat liver tRNA and effect of chemical carcinogens

    SciTech Connect

    Kanduc, D.; Quagliariello, E. )

    1991-07-01

    The interaction of (35S)methionine with hepatic tRNA in normal, carcinogen-treated, and partially hepatectomized rats was studied. tRNA was preferentially labeled following (35S)methionine (1.6 mCi, 25 mg/kg body wt) administration by intraperitoneal injection. The extent of (35S)methionine-tRNA interaction was impaired by partial hepatectomy and by conditions having a carcinogenic potential.

  10. Bracken fern (Pteridium spp.) carcinogenicity and human health--a brief review.

    PubMed

    Smith, B L; Seawright, A A

    1995-01-01

    Bracken fern (Pteridium spp.), one of the most abundant plants on the planet, is well known to cause cancer naturally in sheep and cattle. It contains, in some locations, extremely high concentrations of ptaquiloside which almost certainly is its major carcinogen. Ptaquiloside is transferred through milk. There is epidemiological evidence that the bracken carcinogen, in special situations, may cause cancer in man. Ptaquiloside and its animal models of carcinogenesis also offer good tools for the study of cancer. PMID:7749576

  11. Binding of environmental carcinogens to asbestos and mineral fibres.

    PubMed Central

    Harvey, G; Pagé, M; Dumas, L

    1984-01-01

    A rapid method has been developed for measuring the binding capacity of asbestos and other mineral fibres for environmental carcinogens. Benzo(alpha)pyrene (B(alpha)P), nitrosonornicotine (NNN), and N-acetyl-2-aminofluorene (NAAF) were assayed in the presence of Canadian grade 4T30 chrysotile, chrysotile A, amosite, crocidolite, glass microfibres, glasswool, attapulgite, and titanium dioxide. Chrysotile binds significantly more carcinogens than the other mineral fibres. This binding assay is reproducible with coefficients of variation of less than 8% and 6% respectively for inter and intra assay. The influence of pH was also studied, and there is good correlation between the carcinogen binding and the charge of the tested mineral fibres. The in vitro cytotoxicity on macrophage like cell line P388D1 and the haemolytic activity of various mineral fibres were also measured; a good correlation was found between the binding capacity and the cytotoxicity of tested mineral fibres on P388D1 cells. These results give some explanations for the reported synergism between exposure to asbestos and the smoking habits of workers. PMID:6331497

  12. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis

    PubMed Central

    Ochieng, Josiah; Nangami, Gladys N.; Ogunkua, Olugbemiga; Miousse, Isabelle R.; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T.; Dong, Chenfang; Zhou, Binhua P.; Brown, Dustin G.; Colacci, Annamaria; Hamid, Roslida A.; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P.; Woodrick, Jordan; Scovassi, Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K.; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H.; Eltom, Sakina E.

    2015-01-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial–mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  13. Lung tumors in strain A mice as a bioassay for carcinogenicity of environmental chemicals

    SciTech Connect

    Stoner, G.D. )

    1991-03-01

    This report describes the protocol for the strain A mouse lung tumor bioassay and summarizes results on selected chemicals that have been tested for carcinogenicity in the assay. The assay is of 6 months duration and can distinguish 2-fold differences in carcinogenic potential of compounds from several chemical classes. Specifically, the assay is sensitive to polycyclic hydrocarbons, nitrosamines and nitrosoureas, carbamates, aflatoxin, certain metals, hydrazines, and others, but is relatively insensitive to aromatic amines, aliphatic halides, and other compounds that are carcinogenic in the rodent liver and/or bladder. Recommendations are made for future studies on the: (1) distribution and metabolism of chemicals in strain A mouse lung tissue and in specific lung cell types; (2) ability of the lung tumor bioassay to detect inhibitors and promoters of carcinogenesis; and (3) use of the assay for testing mixtures of chemicals for carcinogenic activity.

  14. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

    NASA Astrophysics Data System (ADS)

    Takanashi, Seiji; Hara, Kazuo; Aoki, Kaoru; Usui, Yuki; Shimizu, Masayuki; Haniu, Hisao; Ogihara, Nobuhide; Ishigaki, Norio; Nakamura, Koichi; Okamoto, Masanori; Kobayashi, Shinsuke; Kato, Hiroyuki; Sano, Kenji; Nishimura, Naoyuki; Tsutsumi, Hideki; Machida, Kazuhiko; Saito, Naoto

    2012-07-01

    The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.

  15. The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis.

    PubMed

    Ochieng, Josiah; Nangami, Gladys N; Ogunkua, Olugbemiga; Miousse, Isabelle R; Koturbash, Igor; Odero-Marah, Valerie; McCawley, Lisa J; Nangia-Makker, Pratima; Ahmed, Nuzhat; Luqmani, Yunus; Chen, Zhenbang; Papagerakis, Silvana; Wolf, Gregory T; Dong, Chenfang; Zhou, Binhua P; Brown, Dustin G; Colacci, Anna Maria; Hamid, Roslida A; Mondello, Chiara; Raju, Jayadev; Ryan, Elizabeth P; Woodrick, Jordan; Scovassi, A Ivana; Singh, Neetu; Vaccari, Monica; Roy, Rabindra; Forte, Stefano; Memeo, Lorenzo; Salem, Hosni K; Amedei, Amedeo; Al-Temaimi, Rabeah; Al-Mulla, Fahd; Bisson, William H; Eltom, Sakina E

    2015-06-01

    The purpose of this review is to stimulate new ideas regarding low-dose environmental mixtures and carcinogens and their potential to promote invasion and metastasis. Whereas a number of chapters in this review are devoted to the role of low-dose environmental mixtures and carcinogens in the promotion of invasion and metastasis in specific tumors such as breast and prostate, the overarching theme is the role of low-dose carcinogens in the progression of cancer stem cells. It is becoming clearer that cancer stem cells in a tumor are the ones that assume invasive properties and colonize distant organs. Therefore, low-dose contaminants that trigger epithelial-mesenchymal transition, for example, in these cells are of particular interest in this review. This we hope will lead to the collaboration between scientists who have dedicated their professional life to the study of carcinogens and those whose interests are exclusively in the arena of tissue invasion and metastasis. PMID:26106135

  16. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin.

    PubMed

    Bley, Keith; Boorman, Gary; Mohammad, Bashir; McKenzie, Donald; Babbar, Sunita

    2012-08-01

    Human exposure to capsaicin, the most abundant pungent chili pepper component, is ubiquitous. Evaluation of capsaicin's carcinogenic potential has produced variable results in in vitro and in vivo genotoxicity and carcinogenicity assays. The capsaicin tested in older studies was often from pepper plant extracts and included other capsaicinoids and diverse impurities. Recent studies utilizing high-purity capsaicin and standardized protocols provide evidence that the genotoxic and carcinogenic potential of capsaicin is quite low and that the purity of capsaicin is important. Several small epidemiological studies suggest a link between capsaicin consumption and stomach or gall bladder cancer, but contamination of capsaicin-containing foods with known carcinogens renders their interpretation problematic. The postulated ability of capsaicin metabolites to damage DNA and promote carcinogenesis remains unsupported. Anticancer activities of capsaicin have been widely reported, as it inhibits the activity of carcinogens and induces apoptosis in numerous cancer cell lines in vitro and explanted into rodents. Diverse mechanisms have been postulated for capsaicin's anticancer properties. One hypothesis is that inhibition of cytochrome P450 enzymes-particularly CYP2E1-retards carcinogen activation but is contradicted by the low potency of capsaicin for CYP inhibition. The potential for dietary capsaicin to act as a chemopreventative is now widely postulated. PMID:22563012

  17. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF DINITROTOLUENE

    EPA Science Inventory

    Carcinogenicity data for mixed dinitrotoluenes are inadequate. ince the technical grade mixture consists of approximately 75% 2,4-dinitrotoluene and 19.5% 2,6-dinitrotoluene, hazard assessment for the mixture can be based on experimentation with the 2,4-isomer. Dinitrotoluene (mi...

  18. Iron in asbestos chemistry and carcinogenicity

    SciTech Connect

    Hardy, J.A.; Aust, A.E.

    1995-01-01

    This article reviews the various aspects regarding the carcinogenicity of asbestos and associated reactions catalyzed by iron. Attention is focused on the following: structure of asbestos; physical properties of asbestos involved in carcinogenesis; reactions catalyzed by iron; reactions catalyzed by asbestos; fiber inactivation; physiological effects; and mutations and cancer. 183 refs.

  19. New public QSAR model for carcinogenicity

    PubMed Central

    2010-01-01

    Background One of the main goals of the new chemical regulation REACH (Registration, Evaluation and Authorization of Chemicals) is to fulfill the gaps in data concerned with properties of chemicals affecting the human health. (Q)SAR models are accepted as a suitable source of information. The EU funded CAESAR project aimed to develop models for prediction of 5 endpoints for regulatory purposes. Carcinogenicity is one of the endpoints under consideration. Results Models for prediction of carcinogenic potency according to specific requirements of Chemical regulation were developed. The dataset of 805 non-congeneric chemicals extracted from Carcinogenic Potency Database (CPDBAS) was used. Counter Propagation Artificial Neural Network (CP ANN) algorithm was implemented. In the article two alternative models for prediction carcinogenicity are described. The first model employed eight MDL descriptors (model A) and the second one twelve Dragon descriptors (model B). CAESAR's models have been assessed according to the OECD principles for the validation of QSAR. For the model validity we used a wide series of statistical checks. Models A and B yielded accuracy of training set (644 compounds) equal to 91% and 89% correspondingly; the accuracy of the test set (161 compounds) was 73% and 69%, while the specificity was 69% and 61%, respectively. Sensitivity in both cases was equal to 75%. The accuracy of the leave 20% out cross validation for the training set of models A and B was equal to 66% and 62% respectively. To verify if the models perform correctly on new compounds the external validation was carried out. The external test set was composed of 738 compounds. We obtained accuracy of external validation equal to 61.4% and 60.0%, sensitivity 64.0% and 61.8% and specificity equal to 58.9% and 58.4% respectively for models A and B. Conclusion Carcinogenicity is a particularly important endpoint and it is expected that QSAR models will not replace the human experts opinions

  20. Identification of carcinogens in cooking oil fumes.

    PubMed

    Chiang, T A; Wu, P F; Ko, Y C

    1999-07-01

    According to earlier studies, fumes from cooking oils were found to be genotoxic in several short-term tests such as the Ames test, sister chromatid exchange, and SOS chromotest. Fume samples from six different commercial cooking oils (safflower, olive, coconut, mustard, vegetable, and corn) frequently used in Taiwan were collected. Polycyclic aromatic hydrocarbons (PAHs) were extracted from the air samples and identified by high-performance liquid chromatography and confirmed by gas chromatography/mass spectrometry. Extracts of fumes from safflower oil, vegetable oil, and corn oil contained benzo[a]pyrene (BaP), dibenz[a,h]anthracene (DBahA), benzo[b]fluoranthene (BbFA), and benzo[a]anthracene (BaA). Concentrations of BaP, DbahA, BbFA, and BaA were 2.1, 2.8, 1.8, and 2.5 microg/m3 in fumes from safflower oil; 2.7, 3.2, 2.6, and 2.1 microg/m3 in vegetable oil; and 2.6, 2.4, 2.0, and 1.9 microg/m3 in corn oil, respectively. The authors constructed models to study the efficacy of table-edged fume extractors used commonly by Taiwanese restaurants. Concentrations of BaP were significantly decreased when the fume extractor was working (P<0.05) and the average reduction in percentage was 75%. The other identified PAHs were undetected. These results indicated that exposure to cooking oil fumes could possibly increase exposure to PAHs, which may be linked to an increased risk of lung cancer. The potential carcinogenic exposure could be reduced by placing table-edged fume extractors near cooking pots. PMID:10361022

  1. Evaluation of carcinogenic responses in the Eker rat following short-term exposure to selected nephrotoxins and carcinogens.

    PubMed

    Morton, Laura Dill; Youssef, Ashraf F; Lloyd, Eric; Kiorpes, Anthony L; Goldsworthy, Thomas L; Fort, Farrel L

    2002-01-01

    This study examined the response of the Eker rat to nephrotoxic compounds and to genotoxic nonrenal carcinogens. Groups of male Eker rats received either no treatment; a vehicle treatment; treatment with a noncarcinogenic nephrotoxin (aluminum nitrilotriacetate, 2 mg/kg/day of aluminum, intraperitoneally, 3 days per week or cyclosporine A, 30 mg/kg/day, orally by gavage, 7 days/week); or treatment with a genotoxic nonrenal carcinogen (furan, 8 mg/kg/day, orally by gavage, 5 days/week or 2,4-diaminotoluene, 6.5 mg/kg/day, orally by gavage, 7 days/week or 2-nitropropane, 89 mg/kg/day, orally by gavage, 3 days/week). Duration of treatment was 4 and/or 6 months. Tissues from the Eker rats were evaluated microscopically and numbers of proliferative renal lesions were counted. Administration of nephrotoxic compounds (Al-NTA and cyclosporine) significantly increased the number of preneoplastic and neoplastic renal lesions in the Eker rat compared to concurrent vehicle controls. The genotoxic nonrenal carcinogens had no consistent effect on numbers of preneoplastic or neoplastic renal lesions and did not produce neoplasms in the expected target organ (liver). PMID:12371664

  2. Carcinogen-mediated methotrexate resistance and dihydrofolate reductase amplification in Chinese hamster cells

    SciTech Connect

    Kleinberger, T.; Etkin, S.; Lavi, S.

    1986-06-01

    We have investigated different parameters characterizing carcinogen-mediated enhancement of methotrexate resistance in Chinese hamster ovary (CHO) cells and in simian virus 40-transformed Chinese hamster embryo (C060) cells. We show that this enhancement reflects dihydrofolate reductase (dhfr) gene amplification. The carcinogens used in this work are alkylating agents and UV irradiation. Both types of carcinogens induce a transient enhancement of methotrexate resistance which increases gradually from the time of treatment to 72 to 96 h later and decreases thereafter. Increasing doses of carcinogens decrease cell survival and increase the enhancement of methotrexate resistance. Enhancement was observed when cells were treated at different stages in the cell cycle, and it was maximal when cells were treated during the early S phase. These studies of carcinogen-mediated dhfr gene amplification coupled with our earlier studies on viral DNA amplification in simian virus 40-transformed cells demonstrate that the same parameters characterize the amplification of both genes. Possible cellular mechanisms responsible for the carcinogen-mediated gene amplification phenomenon are discussed.

  3. Effect of DNA type on response of DNA biosensor for carcinogens

    NASA Astrophysics Data System (ADS)

    Sani, Nor Diyana bt. Md.; Heng, Lee Yook; Surif, Salmijah; Lazim, Azwani Mat

    2013-11-01

    Carcinogens are cancer causing chemicals that can bind to DNA and cause damage to the DNA. These chemicals are available everywhere including in water, air, soil and food. Therefore, a sensor that can detect the presence of these chemicals will be a very useful tool. Since carcinogens bind to DNA, DNA can be used as the biological element in a biosensor. This study has utilized different types of DNA in a biosensor for carcinogen detection. The DNAs include double stranded calf thymus DNA, single stranded calf thymus DNA and guanine rich single stranded DNA. The modified SPE was exposed to a carcinogen followed by interaction with methylene blue which acts as the electroactive indicator. The SPE was then analysed using differential pulse voltammetry (DPV). Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, as well as effect of buffer concentration, buffer pH and ionic strength. The performance of the biosensor was tested on a group 1 carcinogen, formaldehyde. The results indicated that the usage of guanine rich single stranded DNA also gives higher response as carcinogens prefer to bind with guanine compared to other bases.

  4. Prediction of the carcinogenicity of a second group of organic chemicals undergoing carcinogenicity testing

    SciTech Connect

    Zhang, Y.P.; Sussman, N.; Macina, O.T.

    1996-10-01

    Twenty-four organic compounds currently undergoing testing within cancer bioassays under the aegis of the U.S. National Toxicology Program (NTP) were submitted to the computer automated structure evaluation (CASE) and multiple computer automated structure evaluation (MULTICASE) system for predictions of activity. Individual predictions resulting from the NTP combined rodent, NTP mouse, Carcinogenic Potency Database (CPDB) combined rodent, and CPDB mouse databases were combined using Bayes` theorem to yield an overall probability of rodent carcinogenicity. 17 refs., 2 figs., 5 tabs.

  5. Study of the mechanism of carcinogenesis by carcinogens which are negative in the Ames test. Progress report. [ICE; TUMOR PROMOTERS; PROGESTERONE; QUANTITY RATIO; RATS

    SciTech Connect

    Borek, E

    1980-01-01

    Research progress for 1980 is reported. The role of tRNA methyltransferases in two-1 stage carcinogenesis of mice by phorbol esters has been investigated. The mechanisms of elevation of progesterone levels in the rat by ethionine have also beed studied. (ACR)

  6. Determination of DNA adducts by combining acid-catalyzed hydrolysis and chromatographic analysis of the carcinogen-modified nucleobases.

    PubMed

    Leung, Elvis M K; Deng, Kailin; Wong, Tin-Yan; Chan, Wan

    2016-01-01

    The commonly used method of analyzing carcinogen-induced DNA adducts involves the hydrolysis of carcinogen-modified DNA samples by using a mixture of enzymes, followed by (32)P-postlabeling or liquid chromatography (LC)-based analyses of carcinogen-modified mononucleotides/nucleosides. In the present study, we report the development and application of a new approach to DNA adduct analysis by combining the H(+)/heat-catalyzed release of carcinogen-modified nucleobases and the use of LC-based methods to analyze DNA adducts. Results showed that heating the carcinogen-modified DNA samples at 70 °C for an extended period of 4 to 6 h in the presence of 0.05% HCl can efficiently induce DNA depurination, releasing the intact carcinogen-modified nucleobases for LC analyses. After optimizing the hydrolysis conditions, DNA samples with C8- and N (2) -modified 2'-deoxyguanosine, as well as N (6) -modified 2'-deoxyadenosine, were synthesized by reacting DNA with 1-nitropyrene, acetaldehyde, and aristolochic acids, respectively. These samples were then hydrolyzed, and the released nucleobase adducts were analyzed using LC-based analytical methods. Analysis results demonstrated a dose-dependent release of target DNA adducts from carcinogen-modified DNA samples, indicating that the developed H(+)/heat-catalyzed hydrolysis method was quantitative. Comparative studies with enzymatic digestion method on carcinogen-modified DNA samples revealed that the two hydrolysis methods did not yield systematically different results. PMID:26581621

  7. Environmental carcinogens and mutational pathways in atherosclerosis.

    PubMed

    Pulliero, A; Godschalk, R; Andreassi, M G; Curfs, D; Van Schooten, F J; Izzotti, A

    2015-05-01

    Atherosclerosis is associated with DNA damage in both circulating and vessel-wall cells and DNA adducts derived from exposure to environmental mutagens are abundant in atherosclerotic vessels. Environmental chemical carcinogens identified as risk factor for atherosclerosis include polycyclic aromatic hydrocarbons (benzo(a)pyrene, dimethylbenz(a)anthracene, beta-naphthoflavone, pyrene, 3-methylcolanthrene), arsenic, cadmium, 1,3-butadiene, cigarette smoke. Accordingly, polymorphisms of genes encoding for phase I/II metabolic reaction and DNA repair are risk factor for cardiovascular diseases, although their role is negligible as compared to other risk factors. The pathogenic relevance of mutation-related molecular damage in atherosclerosis has been demonstrated in experimental animal models involving the exposure to chemical mutagens. The relevance of mutation-related events in worsening atherosclerosis prognosis has been demonstrated in human clinical studies mainly as referred to mitochondrial DNA damage. Atherosclerosis is characterized by the occurrence of high level of oxidative damage in blood vessel resulting from both endogenous and exogenous sources. Mitochondrial damage is a main endogenous source of oxidative stress whose accumulation causes activation of intrinsic apoptosis through BIRC2 inhibition and cell loss contributing to plaque development and instability. Environmental physical mutagens, including ionizing radiation, are a risk factor for atherosclerosis even at the low exposure dose occurring in case of occupational exposure or the high exposure doses occurring during radiotherapy. Conversely, the role of exciting UV radiation in atherosclerosis is still uncertain. This review summarizes the experimental and clinical evidence supporting the pathogenic role of mutation-related pathway in atherosclerosis examining the underlying molecular mechanisms. PMID:25704189

  8. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

    PubMed Central

    Huff, J E; Haseman, J K; DeMarini, D M; Eustis, S; Maronpot, R R; Peters, A C; Persing, R L; Chrisp, C E; Jacobs, A C

    1989-01-01

    Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence

  9. A study protocol for the evaluation of occupational mutagenic/carcinogenic risks in subjects exposed to antineoplastic drugs: a multicentric project

    PubMed Central

    2011-01-01

    Background Some industrial hygiene studies have assessed occupational exposure to antineoplastic drugs; other epidemiological investigations have detected various toxicological effects in exposure groups labeled with the job title. In no research has the same population been studied both environmentally and epidemiologically. The protocol of the epidemiological study presented here uses an integrated environmental and biological monitoring approach. The aim is to assess in hospital nurses preparing and/or administering therapy to cancer patients the current level of occupational exposure to antineoplastic drugs, DNA and chromosome damage as cancer predictive effects, and the association between the two. Methods/Design About 80 healthy non-smoking female nurses, who job it is to prepare or handle antineoplastic drugs, and a reference group of about 80 healthy non-smoking female nurses not occupationally exposed to chemicals will be examined simultaneously in a cross-sectional study. All the workers will be recruited from five hospitals in northern and central Italy after their informed consent has been obtained. Evaluation of surface contamination and dermal exposure to antineoplastic drugs will be assessed by determining cyclophosphamide on selected surfaces (wipes) and on the exposed nurses' clothes (pads). The concentration of unmetabolized cyclophosphamide as a biomarker of internal dose will be measured in end-shift urine samples from exposed nurses. Biomarkers of effect and susceptibility will be assessed in exposed and unexposed nurses: urinary concentration of 8-hydroxy-2-deoxyguanosine; DNA damage detected using the single-cell microgel electrophoresis (comet) assay in peripheral white blood cells; micronuclei and chromosome aberrations in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e. glutathione S-transferases) will also be analysed. Using standardized questionnaires, occupational exposure will

  10. Risk assessment of DNA-reactive carcinogens in food

    SciTech Connect

    Jeffrey, A.M. . E-mail: Alan_Jeffrey@nymc.edu; Williams, G.M.

    2005-09-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B{sub 1} (AFB{sub 1}), a limit of 20 ppb or {approx}30 {mu}g/day has been set and is considered a tolerable daily intake (TDI). Since AFB{sub 1} is considered a potent carcinogen, doses of <1.5 {mu}g of unknown compounds are considered TDIs. Most DNA-reactants, including acrylamide, heterocyclic amines, and {alpha},{beta}-unsaturated carbonyl are below this value. Above that value, measurement of actual DNA adducts levels in either experimental animals with a risk assessment, or, when this occurs, exposed humans are needed. A number of approaches to undertake this are described including immunological, mass spectrometric and {sup 32}P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the

  11. Medium-term bioassays for carcinogenicity of chemical mixtures.

    PubMed Central

    Ito, N; Imaida, K; Hirose, M; Shirai, T

    1998-01-01

    Carcinogenic effects of chemical mixtures were examined with a medium-term liver bioassay for carcinogens or a multiorgan medium-term bioassay using male F344 rats. In the medium-term liver bioassay, rats were initially treated with diethylnitrosamine (DEN) at 200 mg/kg body weight, i.p.; after 2 weeks they received chemical mixtures such as 10 different heterocyclic amines at one-tenth or one-hundredth the dose levels used in carcinogenicity studies and the mixtures of 20 different pesticides, each at acceptable daily intake (ADI) levels or a mixture of 100 times ADI levels. All animals were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. The number and areas of glutathione S-transferase placental form (GST-P) positive foci (preneoplastic lesions in the liver) were compared between respective groups. When 10 heterocyclic amines were mixed in the diet at one-tenth dose level, clear synergism was observed, but no combined effects were evident with the one-hundredth dose levels. In the pesticide experiment, treatment of rats with the 20-pesticide mixture at the ADI dose level did not enhance GST-P-positive foci. In contrast, a mixture of 100 times the ADI significantly increased those values. In a multiorgan bioassay of 28 weeks, mixtures of 40 high-volume compounds and 20 pesticides (suspected carcinogens) added together at their respective ADI levels did not enhance carcinogenesis in any organs initiated by five different carcinogens (DEN, N-methylnitrosourea, dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)nitrosamine, and dihydroxy-di-n-propylnitrosamine) in combination. The combination effect of low dietary levels of five antioxidants, butylated hydroxyanisole, caffeic acid, sesamol, 4-methoxyphenol, and catechol, were also examined using the multiorgan bioassay. The incidence of forestomach papillomas was significantly increased only in the combination group and the results indicate that combination of the five antioxidants can

  12. [Strategy in directed preventive studies. I. Evaluation of health effects of exposure to carcinogenic factors. Problem of development- al anomalies and neoplasms in children. Reproduction disorders].

    PubMed

    Indulski, J A; Kowalski, Z

    1990-01-01

    In highly developed countries the prophylactic medical examinations to evaluate health effects of exposure and general health condition of the workers started early in the past. Nowadays, there is an increasing trend of developing new methods for early detection of occupational and work--related diseases. Thus the individuals oversensitive to the agents of the working environment could be prevented from exposure. However, the gap between the capacities that the new methods offer theoretically and their actual application in the prophylactic examinations still remains quite large. Part I of the present study has been devoted to three essential problems of public concern which have been specified in the paper's subtitles. PMID:2131393

  13. Assessment of the carcinogenicity of the nonnutritive sweetener cyclamate.

    PubMed

    Ahmed, F E; Thomas, D B

    1992-01-01

    The weight of the evidence from metabolic studies, short-term tests, animal bioassays, and epidemiological studies indicates that cyclamate (CHS) is not carcinogenic by itself; however, there is evidence from in vitro and in vivo studies in animals that implies it may have cancer-promoting or cocarcinogenic activity. Epidemiological studies indicate that the use of nonnutritive sweeteners (CHS and saccharin) has not resulted in a measurable overall increase in the risk of bladder cancer in individuals who have ever used these products. No epidemiological information exists on the possible associations of these sweeteners and cancers other than those of the urinary tract. It is recommended that (1) no further studies on the metabolism of CHS to evaluate its carcinogenicity are required since no potentially hazardous metabolites have been appreciably detected in humans; (2) no further animal bioassays to test for the carcinogenicity of CHS by itself are necessary; (3) the studies in rodents that suggest a promotional or cocarcinogenic effect of CHS should be repeated because they cannot be ruled out; (4) because the significance to human health of a positive outcome of such studies is uncertain, additional research aimed at understanding the predictive value for human health of such results and more generic studies to develop well-validated systems that can be relied on in the assessment of cancer-promoting agents are recommended; (5) in populations where CHS continues to be used, epidemiological monitoring should be continued to determine whether there is an increased risk of cancer in humans who are heavy or long-term users or for those observed long after first exposure. In such monitoring, other cancer sites--in addition to the bladder--should be considered. PMID:1510820

  14. Epigenetic events during the process of cell transformation induced by carcinogens (review).

    PubMed

    Nguyen-Ba, G; Vasseur, P

    1999-01-01

    Recent studies clearly demonstrate that several environmental carcinogens lack the ability to initially induce genetic damage. In that view, multistage chemical carcinogenesis may be processed under the control of a variety of epigenetic events in addition to genotoxic impacts. The understanding of this mechanism as reviewed in this report requires knowledge of early changes induced by carcinogens in target cells, biochemical, biological and molecular reactions closely related to both sides of the growth equation: cell proliferation and programmed death. Among several cell transformation models, the most suitable for carcinogen detection and mechanistic study is the Syrian hamster embryo (SHE) cell transformation assay. This closely mimics the multistage carcinogenesis and we can examine, in a relatively short time (8 days), the mechanisms by which genotoxic and non-genotoxic agents may increase the frequency of cell transformation as a preneoplastic end-point. The mode of action of hundred of compounds, carcinogens and non-carcinogens, has been explored so far using one-stage and two-stage treatment protocols. In general, with the two-stage protocol, all carcinogens, irrespective of their genotoxic or non-genotoxic potential, give unambiguous positive results. Since perturbations of cell proliferation and death are considered essential events in the process of carcinogenesis, studies have been conducted on the dysregulation of two specific parameters, the induction of ornithine decarboxylase (ODC) an enzyme related to cell proliferation, and the apoptosis rate, when SHE cells are exposed to carcinogens. In one-stage treatment (5 h-24 h), only the promoter TPA induces ODC activity, while other carcinogens do not increase this activity. Using the two-stage exposure protocol (1 h xenobiotic/5 h TPA), all carcinogens both genotoxic and non-genotoxic, are able to stimulate ODC activity above the level obtained with TPA alone. Based on the two-stage treatment with

  15. A study on the carcinogenicity of human diets in rats: the influence of heating and the addition of vegetables and fruit.

    PubMed

    Alink, G M; Kuiper, H A; Beems, R B; Koeman, J H

    1989-07-01

    The influence of dietary factors such as total composition, thermal processing, and the addition of vegetables and fruit on the tumour rate in rats was studied in a long-term experiment. Groups of 50 male and 50 female Wistar rats were fed one of the following diets: a semi-synthetic animal diet (A, control); diet A to which vegetables and fruit were added (B); an uncooked human diet (meat, bread and eggs) supplemented with semi-synthetic compounds (C); diet C with fried or baked products (D); a complete human diet consisting of heated products, vegetables and fruit prepared according to mean consumption figures in The Netherlands (E). The animal diets (A and B) contained 26.0 energy (E)% protein, 21.6 E% fat, 52.4 E% carbohydrate and 10.7% (w/w) fibre. The human diets contained 13.2 E% protein, 40.6 E% fat, 46.2 E% carbohydrate and 5% (w/w) fibre. The rats were fed ad lib. for 142 wk. In males and females fed human diets (C, D or E) hepatocellular vacuolization was observed. Male rats (but not female) fed the human diet had a significantly (P less than 0.02) higher incidence of epithelial tumours than those fed the animal diet. This increase was mainly due to tumours of the pituitary and thyroid. Frying and baking of food products (diet D) and the addition of vegetables and fruit (diet E) induced minor differences in tumour rate, but they were not statistically significant. PMID:2777146

  16. Species and gender differences in the carcinogenic activity of trimethylolpropane triacrylate in rats and mice

    PubMed Central

    Surh, Inok; Rao, Deepa B.; Cesta, Mark F.; Hébert, Charles D.; Mann, Jill F.; Cunny, Helen; Kissling, Grace E.; Malarkey, David; Chhabra, Rajendra S.

    2014-01-01

    Trimethylolpropane triacrylate (TMPTA) is a multifunctional monomer with industrial applications. To determine the carcinogenic potential, male and female F344/N rats and B6C3F1/N mice were administered TMPTA (0, 0.3, 1.0, or 3.0 mg/kg) in acetone dermally for 2 years. There were no differences in the body weights and survival in the treated animals compared to controls. Nonneoplastic skin lesions at the site of application included epidermal hyperplasia and hyperkeratosis in both rats and mice. There were no incidences of tumors at the site of application in rats and mice. Rare malignant liver neoplasms were observed in female mice that included hepatoblastoma in the 0.3 and 3.0 mg/kg groups, and hepatocholangiocarcinoma in the 1.0 and 3.0 mg/kg groups. The incidences of uterine stromal polyp and stromal polyp or stromal sarcoma (combined) in female mice occurred with positive trends and the incidences were significantly increased in the 3.0 mg/kg group. A marginal increase in the incidences of malignant mesothelioma in male rats may have been related to TMPTA treatment. In conclusion, our studies show that TMPTA is a dermal irritant in both rats and mice of either sex. Increased incidences of tumor formation were observed in female mice and male rats. PMID:24503412

  17. Assessment of the carcinogenic potential of polyglycerol polyricinoleate (PGPR) in rats and mice.

    PubMed

    Smith, M R; Wilson, R; Hepburn, P A

    1998-01-01

    The carcinogenic potential of the food emulsifier ADMUL WOL brand of polyglycerol polyricinoleate (PGPR) was evaluated in rats and mice. Groups of 60 male and 60 female rats were given purified diets containing 5% of either PGPR or groundnut oil for 2 years. Groups of 25 male and 25 female mice were given purified diets containing 5% of either PGPR or groundnut oil for 80 weeks. No carcinogenic effect of PGPR was observed. In addition, dietary PGPR had no adverse effect on growth, food consumption, longevity and haematology. Organ weight analysis revealed an increase in liver and kidney weight in both male and female rats and female mice. Histological analysis of tissues revealed no treatment related adverse effects. PMID:9737421

  18. Phthalate esters as peroxisome proliferator carcinogens.

    PubMed Central

    Warren, J R; Lalwani, N D; Reddy, J K

    1982-01-01

    The phthalate ester di(2-ethylhexyl) phthalate is both a peroxisome proliferator and a hepatic carcinogen. Peroxisome proliferators as a class are hepatocarcinogenic in rodent species. However, none of the peroxisome proliferators tested to date including the phthalate esters and related alcohol and acid analogs have demonstrated mutagenic or DNA-damaging activity in the in vitro Salmonella typhimurium/microsomal or the lymphocyte 3H-thymidine assays. A working hypothesis is proposed that peroxisome proliferation itself initiates neoplastic transformation of hepatic parenchymal cells by increasing intracellular rates of DNA-damaging reactive oxygen production. Evidence which supports such a hypothesis includes increased fatty acid beta-oxidation, elevated H2O2 levels, accumulation of peroxidized lipofuscin, disproportionately small increase in catalase, and elevated peroxisomal uricase activity which accompany peroxisome proliferation in hepatocytes. Direct testing of this hypothesis will provide insight into mechanisms of phthalate ester carcinogenicity and cytotoxicity. Images FIGURE 1. PMID:6754363

  19. Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

    SciTech Connect

    Venkatapathy, Raghuraman Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

    2009-01-15

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD{sub 50}]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD{sub 50}) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD{sub 50} and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD{sub 50}s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD{sub 50} for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction.

  20. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    PubMed

    Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

    2010-10-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

  1. Impact and compliance: OSHA Carcinogen Policy

    SciTech Connect

    Meyer, A.F. Jr.; Crowder, C.; Wisniewski, S.; Russell, T.; Senn, K.

    1980-06-26

    This document provides an examination of various aspects of the Occupational Safety and Health Administration (OSHA)Carcinogen Policy. To satisfy the dimensions of the Policy's broad, general nature, a two-fold approach was taken. Throughout, the focus is on the possible effects of the Policy's implementation, but this is first approached as it generally will effect research and compliance activities across broad industry sectors, while specific impacts on DOE are addressed separately. To overview and integrate these approaches, and to provide a quick reference for further information, an outline of information is presented. General or industry-wide applications are addressed both in the Summary and Overview of the Policy (Chapters I and II) and in the discussion of the Model Standard (Chapter V). Also included is a copy of the Policy itself in the General Industry Standards and interpretations Change 10. Sections specifically addressed to the major concerns of DOE and its contractors are a discussion of implications for action regarding the synthetic fuels program, a comparison of the OSHA Model Regulations and the FE OSH Manual Standards for Carcinogens, and finally, a list of known carcinogens in coal gasification/liquefaction. Together, these elements illustrate the broad scope of the policy's impact, which economic and other constraining consequences begin to become visible. Measures to minimize these consequences are a common underlying theme to each of the sections.

  2. Carcinogenic potential of hydrotreated petroleum aromatic extracts.

    PubMed

    Doak, S M; Hend, R W; van der Wiel, A; Hunt, P F

    1985-06-01

    Five experimental petroleum extracts were produced from luboil distillates derived from Middle East paraffinic crude by solvent extraction and severe hydrotreatment. The polycyclic aromatic content (PCA) of the extracts was determined by dimethyl sulphoxide extraction and ranged from 3.7-9.2% w/w. The five extracts were evaluated for their potential to induce cutaneous and systemic neoplasia in female mice derived from Carworth Farm No 1 strain (CF1). The test substances were applied undiluted (0.2 ml per application) to the shorn dorsal skin twice weekly for up to 78 weeks, with 48 mice in each treatment group and 96 in the untreated control group; two further groups, each of 48 mice, were similarly treated either with a non-hydrotreated commercial aromatic extract (PCA content, 19.7% w/v) or with a low dose of benzo(a)pyrene (12.5 micrograms/ml acetone). The mice were housed individually in polypropylene cages in specified pathogen free conditions. The incidence of cutaneous and systemic tumours was determined from histological analysis of haematoxylin and eosin stained tissue sections. The results were correlated with the PCA content of the extracts and compared with those from female mice exposed to a non-hydrotreated commercial aromatic extract. Four of the hydrotreated extracts were carcinogenic for murine skin; the two products with the lower PCA contents were less carcinogenic than the products with the higher PCA contents and all were less carcinogenic than the commercial extract. One extract with the lowest PCA content was non-carcinogenic. Thus refining by severe hydrotreatment was an effective method of reducing the carcinogenic potential of petroleum aromatic extracts. Although other physicochemical properties may influence the biological activity of oil products, the PCA content determined by dimethyl sulphoxide extraction may be a useful indicator of the potential of oil products to induce cutaneous tumours in experimental animals. There was no

  3. Hematotoxicity and carcinogenicity of benzene

    SciTech Connect

    Aksoy, M. )

    1989-07-01

    The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of the series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of the series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.

  4. [Advances in non-carcinogenic toxicity of trichloroethylene].

    PubMed

    Huang, Peiwu; Li, Xuan; Liu, Wei; Liu, Jianjun

    2015-09-01

    Trichloroethylene (TCE) is a widely used organic solvent and an important industrial material. Due to mass production and use, and improper waste disposal, TCE has become a common environmental contaminant, so there is a wide range of occupationally and environmentally exposed population. Occupational and environmental exposure to TCE can produce toxic effects on multiple organs and systems. This paper is a review of the immunotoxicity, reproductive toxicity, neurotoxicity, teratogenic effect and other non-carcinogenic toxic effects of TCE from the aspects of epidemiological study, experimental evidence on animals and toxic mechanisms. PMID:26733146

  5. Differential display in rat livers treated for 13 weeks with phenobarbital implicates a role for metabolic and oxidative stress in nongenotoxic carcinogenicity.

    PubMed

    Elrick, Mollisa M; Kramer, Jeffrey A; Alden, Carl L; Blomme, Eric A G; Bunch, Roderick T; Cabonce, Marc A; Curtiss, Sandra W; Kier, Larry D; Kolaja, Kyle L; Rodi, Charles P; Morris, Dale L

    2005-01-01

    Hepatic enzyme inducers such as phenobarbital are often nongenotoxic rodent hepatocarcinogens. Currently, nongenotoxic hepatocarcinogens can only be definitively identified through costly and extensive long-term, repeat-dose studies (e.g., 2-year rodent carcinogenicity assays). Although liver tumors caused by these compounds are often not found to be relevant to human health, the mechanism(s) by which they cause carcinogenesis are not well understood. Toxicogenomic technologies represent a new approach to understanding the molecular bases of toxicological liabilities such asnongenotoxic carcinogenicity early in the drug discovery/development process. Microarrays have been used to identify mechanistic molecular markers of nongenotoxic rodent hepatocarcinogenesis in short-term, repeat-dose preclinical safety studies. However, the initial "noise" of early adaptive changes may confound mechanistic interpretation of transcription profiling data from short-term studies, and the molecular processes triggered by treatment with a xenobiotic agent are likely to change over the course of long-term treatment. Here, we describe the use of a differential display technology to understand the molecular mechanisms related to 13 weeks of dosing with the prototype rodent nongenotoxic hepatocarcinogen, phenobarbital. These findings implicate a continuing role for oxidative stress in nongenotoxic carcinogenicity.An Excel data file containing raw data is available in full at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. Click on the issue link for 33(1), then select this article. A download option appears at the bottom of this abstract. The file contains raw data for all gene changes detected by AFLP, including novel genes and genes of unknown function; sequences of detected genes; and animal body and liver weight ratios. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through

  6. HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life.

    PubMed

    Nduati, Eunice W; Nkumama, Irene N; Gambo, Faith K; Muema, Daniel M; Knight, Miguel G; Hassan, Amin S; Jahangir, Margaret N; Etyang, Timothy J; Berkley, James A; Urban, Britta C

    2016-07-01

    Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected. PMID:27170641

  7. The association of maternal vitamin D status with infant birth outcomes, postnatal growth and adiposity in the first 2 years of life in a multi-ethnic Asian population: the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study.

    PubMed

    Ong, Yi Lin; Quah, Phaik Ling; Tint, Mya Thway; Aris, Izzuddin M; Chen, Ling Wei; van Dam, Rob M; Heppe, Denise; Saw, Seang-Mei; Godfrey, Keith M; Gluckman, Peter D; Chong, Yap Seng; Yap, Fabian; Lee, Yung Seng; Foong-Fong Chong, Mary

    2016-08-01

    Maternal vitamin D status during pregnancy has been associated with infant birth and postnatal growth outcomes, but reported findings have been inconsistent, especially in relation to postnatal growth and adiposity outcomes. In a mother-offspring cohort in Singapore, maternal plasma vitamin D was measured between 26 and 28 weeks of gestation, and anthropometric measurements were obtained from singleton offspring during the first 2 years of life with 3-month follow-up intervals to examine birth, growth and adiposity outcomes. Associations were analysed using multivariable linear regression. Of a total of 910 mothers, 13·2 % were vitamin D deficient (<50 nmol/l) and 26·5 % were insufficient (50-75 nmol/l). After adjustment for potential confounders and multiple testing, no statistically significant associations were observed between maternal vitamin D status and any of the birth outcomes - small for gestational age (OR 1·00; 95 % CI 0·56, 1·79) and pre-term birth (OR 1·16; 95 % CI 0·64, 2·11) - growth outcomes - weight-for-age z-scores, length-for-age z-scores, circumferences of the head, abdomen and mid-arm at birth or postnatally - and adiposity outcomes - BMI, and skinfold thickness (triceps, biceps and subscapular) at birth or postnatally. Maternal vitamin D status in pregnancy did not influence infant birth outcomes, postnatal growth and adiposity outcomes in this cohort, perhaps due to the low prevalence (1·6 % of the cohort) of severe maternal vitamin D deficiency (defined as of <30·0 nmol/l) in our population. PMID:27339329

  8. HIV-Exposed Uninfected Infants Show Robust Memory B-Cell Responses in Spite of a Delayed Accumulation of Memory B Cells: an Observational Study in the First 2 Years of Life

    PubMed Central

    Nkumama, Irene N.; Gambo, Faith K.; Muema, Daniel M.; Hassan, Amin S.; Jahangir, Margaret N.; Etyang, Timothy J.; Berkley, James A.; Urban, Britta C.

    2016-01-01

    Improved HIV care has led to an increase in the number of HIV-exposed uninfected (HEU) infants born to HIV-infected women. Although they are uninfected, these infants experience increased morbidity and mortality. One explanation may be that their developing immune system is altered by HIV exposure, predisposing them to increased postnatal infections. We explored the impact of HIV exposure on the B-cell compartment by determining the B-cell subset distribution, the frequency of common vaccine antigen-specific memory B cells (MBCs), and the levels of antibodies to the respective antigens in HEU and HIV-unexposed uninfected (HUU) infants born to uninfected mothers, using flow cytometry, a B-cell enzyme-linked immunosorbent spot assay, and an enzyme-linked immunosorbent assay, respectively, during the first 2 years of life. For the majority of the B-cell subsets, there were no differences between HEU and HUU infants. However, HIV exposure was associated with a lower proportion of B cells in general and MBCs in particular, largely due to a lower proportion of unswitched memory B cells. This reduction was maintained even after correcting for age. These phenotypic differences in the MBC compartment did not affect the ability of HEU infants to generate recall responses to previously encountered antigens or reduce the antigen-specific antibody levels at 18 months of life. Although HIV exposure was associated with a transient reduction in the proportion of MBCs, we found that the ability of HEU infants to mount robust MBC and serological responses was unaffected. PMID:27170641

  9. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    PubMed

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment. PMID:26152227

  10. Carcinogenic HPV infection in the cervical squamo-columnar junction.

    PubMed

    Mirkovic, Jelena; Howitt, Brooke E; Roncarati, Patrick; Demoulin, Stephanie; Suarez-Carmona, Meggy; Hubert, Pascale; McKeon, Frank D; Xian, Wa; Li, Anita; Delvenne, Philippe; Crum, Christopher P; Herfs, Michael

    2015-07-01

    Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16(ink4), Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16(ink4) and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16(ink4) immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16(ink4) expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ. PMID:25782708

  11. Voltammetric studies on the potent carcinogen, 7,12-dimethylbenz[a]anthracene: Adsorptive stripping voltammetric determination in bulk aqueous forms and human urine samples and detection of DNA interaction on pencil graphite electrode.

    PubMed

    Yardim, Y; Keskin, E; Levent, A; Ozsöz, M; Sentürk, Z

    2010-01-15

    7,12-Dimethylbenz[a]anthracene (DMBA), is a widely studied polycyclic aromatic hydrocarbon that has long been recognized as a very potent carcinogen. Initially, the electrochemical oxidation of DMBA at the glassy carbon and pencil graphite electrodes in non-aqueous media (dimethylsulphoxide with lithium perchlorate) was studied by cyclic voltammetry. DMBA was irreversibly oxidized in two steps at high positive potentials, resulting in the ill-resolved formation of a couple with a reduction and re-oxidation wave at much lower potentials. Special attention was given to the use of adsorptive stripping voltammetry together with a medium exchange procedure on disposable pencil graphite electrode in aqueous solutions over the pH range of 3.0-9.0. The response was characterized with respect to pH of the supporting electrolyte, pre-concentration time and accumulation potential. Using square-wave stripping mode, the compound yielded a well-defined voltammetric response in acetate buffer, pH 4.8 at +1.15V (vs. Ag/AgCl) (a pre-concentration step being carried out at a fixed potential of +0.60V for 360s). The process could be used to determine DMBA concentrations in the range 2-10nM, with an extremely low detection limit of 0.194nM (49.7ngL(-1)). The applicability to assay of spiked human urine samples was also illustrated. Finally, the interaction of DMBA with fish sperm double-stranded DNA based on decreasing of the oxidation signal of adenine base was studied electrochemically by using differential pulse voltammetry with a pencil graphite electrode at the surface and also in solution. The favorable signal-to-noise characteristics of biosensor resulted in low detection limit (ca. 46nM) following a 300-s interaction. These results displayed that the electrochemical DNA-based biosensor could be used for the sensitive, rapid, simple and cost effective detection of DMBA-DNA interaction. PMID:20006098

  12. Role of Cytochrome P450 Monooxygenase in Carcinogen and Chemotherapeutic Drug Metabolism.

    PubMed

    Wahlang, B; Falkner, K Cameron; Cave, Matt C; Prough, Russell A

    2015-01-01

    The purpose of this chapter is to provide insight into which human cytochromes P450 (CYPs) may be involved in metabolism of chemical carcinogens and anticancer drugs. A historical overview of this field and the development of literature using relevant animal models and expressed human CYPs have provided information about which specific CYPs may be involved in carcinogen metabolism. Definition of the biochemical properties of CYP activity came from several groups who studied the reaction stoichiometry of butter yellow and benzo[α]pyrene, including their role in induction of these enzyme systems. This chapter will list as much as is known about the human CYPs involved in carcinogen and anticancer drug metabolism, as well as summarize studies with rodent CYPs. A review of three major classes of anticancer drugs and their metabolism in humans is covered for cyclophosphamide, procarbazine, and anthracycline antibiotics, cancer chemotherapeutic compounds extensively metabolized by CYPs. The emerging information about human CYP gene polymorphisms as well as other enzymes involved in foreign compound metabolism provides considerable information about how these genetic variants affect carcinogen and anticancer drug metabolism. With information available from individual's genomic sequences, consideration of populations who may be at risk due to environmental exposure to carcinogens or how to optimize their cancer therapy regimens to enhance efficacy of the anticancer drugs appears to be an important field of study to benefit individuals in the future. PMID:26233902

  13. Clinical outcomes of pars plicata anterior vitrectomy: 2-year results

    PubMed Central

    Narang, Priya; Agarwal, Amar

    2015-01-01

    Purpose: To demonstrate the safety and outcome of a surgical approach that uses pars plicata site for anterior vitrectomy during phacoemulsification procedure complicated by posterior capsule rupture and residual cortical matter. Design: Single center, retrospective, interventional, noncomparative study. Materials and Methods: Medical records of a consecutive series of 35 eyes of 35 patients who underwent pars plicata anterior vitrectomy (PPAV) were reviewed. The main outcome measures were corrected and uncorrected distance visual acuity (CDVA, UDVA), early and late postoperative complications and intraocular pressure (IOP). Ultrasound biomicroscopic (UBM) evaluation of sclerotomy site and spectral domain optical coherence tomography analysis for central macular thickness (CMT) was performed. The final visual outcome at 2 years was evaluated. Results: At 2 years follow-up, the mean postoperative UDVA (logarithm of the minimum angle of resolution [logMAR]) and CDVA (logMAR) was 0.49 ± 0.26 and 0.19 ± 0.14, respectively. There was no significant change in the IOP (P = 0.061) and the mean CMT at 2 years was 192.5 ± 5.54 μm. The postoperative UBM image of the sclerotomy site at 8 weeks demonstrated a clear wound without any vitreous adhesion or incarceration. Intraoperative hyphema was seen in 1 (2.8%) case and postoperative uveitis was seen in 2 (5.7%) cases, which resolved with medications. No case of an iatrogenic retinal break or retinal detachment was reported. Conclusions: PPAV enables a closed chamber approach, allows thorough cleanup of vitreous in the pupillary plane and anterior chamber and affords better access to the subincisional and retropupillary cortical remnant with a significant visual outcome and an acceptable complication rate. PMID:26632124

  14. Infantile Amnesia across the Years: A 2-Year Follow-Up of Children's Earliest Memories

    ERIC Educational Resources Information Center

    Peterson, Carole; Warren, Kelly L.; Short, Megan M.

    2011-01-01

    Although infantile amnesia has been investigated for many years in adults, only recently has it been investigated in children. This study was a 2-year follow-up and extension of an earlier study. Children (4-13 years old) were asked initially and 2 years later for their earliest 3 memories. At follow-up, their age at the time of these memories…

  15. Chief Student Affairs Officers in 2-Year Colleges: Their Demographics and Educational Backgrounds

    ERIC Educational Resources Information Center

    Keim, Marybelle C.

    2008-01-01

    The purpose of this study was to determine demographics and educational backgrounds of chief student affairs officers (CSAOs) in public 2-year colleges. Using systematic sampling techniques, 300 2-year colleges were selected from the AACC Membership Directory for inclusion in the study. Each college's website was visited to determine the name of…

  16. Clinical neuroprediction: Amygdala reactivity predicts depressive symptoms 2 years later.

    PubMed

    Mattson, Whitney I; Hyde, Luke W; Shaw, Daniel S; Forbes, Erika E; Monk, Christopher S

    2016-06-01

    Depression is linked to increased amygdala activation to neutral and negatively valenced facial expressions. Amygdala activation may be predictive of changes in depressive symptoms over time. However, most studies in this area have focused on small, predominantly female and homogenous clinical samples. Studies are needed to examine how amygdala reactivity relates to the course of depressive symptoms dimensionally, prospectively and in populations diverse in gender, race and socioeconomic status. A total of 156 men from predominately low-income backgrounds completed an fMRI task where they viewed emotional facial expressions. Left and right amygdala reactivity to neutral, but not angry or fearful, facial expressions relative to a non-face baseline at age 20 predicted greater depressive symptoms 2 years later, controlling for age 20 depressive symptoms. Heightened bilateral amygdala reactivity to neutral facial expressions predicted increases in depressive symptoms 2 years later in a large community sample. Neutral facial expressions are affectively ambiguous and a tendency to interpret these stimuli negatively may reflect to cognitive biases that lead to increases in depressive symptoms over time. Individual differences in amygdala reactivity to neutral facial expressions appear to identify those at most risk for a more problematic course of depressive symptoms across time. PMID:26865423

  17. Dermal carcinogenic activity of petroleum-derived middle distillate fuels.

    PubMed

    Biles, R W; McKee, R H; Lewis, S C; Scala, R A; DePass, L R

    1988-12-30

    In general, the carcinogenic potential of petroleum-derived materials is related to the polycyclic aromatic hydrocarbon (PAH) content. Thus it has been assumed that liquids which boil below the PAH distillation range (i.e., below approx. 370 degrees C (700 degrees F) would not be carcinogenic. Several early studies supported this conclusion but were of relatively short duration. Several recent and more rigorous studies have shown that repeated application of certain petroleum-derived materials boiling between approximately 177-370 degrees C (350-700 degrees F) (i.e., middle distillate fuels) can produce tumors in mouse skin. The current studies assessed the tumorigenic potential of a series of middle distillates which varied with respect to boiling range, composition, and source of blending stocks. All of the samples produced evidence of weak tumorigenic activity which was characterized by low tumor yields and long median latencies. However, the majority of the tumor yields were significantly different from the control. There were no apparent differences in response among the samples. Thus the various parameters examined did not substantially influence tumor outcome. In particular, there was no association of tumorigenic activity with aromatic carbon content; this finding, coupled with evidence that PAH levels were low, suggested that the tumorigenic responses were not PAH-dependent. In addition to the tumors, there was evidence of non-neoplastic dermal changes including hyperplasia. These may have contributed to the tumorigenic responses; however, the actual mechanism of tumor induction is unknown. PMID:3212789

  18. Review of genotoxicity and rat carcinogenicity investigations with astaxanthin.

    PubMed

    Edwards, James A; Bellion, Phillip; Beilstein, Paul; Rümbeli, Robert; Schierle, Joseph

    2016-03-01

    Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance. PMID:26713891

  19. Development of a carcinogenic potency index for dermal exposure to viscous oil products.

    PubMed

    Brandt, H C; Booth, E D; de Groot, P C; Watson, W P

    1999-01-01

    Polycyclic aromatic compounds (PACs) present in oil streams and formulated products are important determinants of possible carcinogenicity. Following dermal exposures the transport of the PACs from oil (the carrier) into the skin is a factor that may affect macromolecular (DNA) adduct formation and thus determine carcinogenicity. We have developed a mathematical model, which describes the flux into the skin for a representative carcinogenic PAC, benzo(a)pyrene. The model is based on measurements of the amount of benzo(a)pyrene bound to skin DNA or blood observed in mouse skin painting studies. The degree of adduct formation from a particular oil product, which we term the Bioavailability Index (BI), was shown to be a function of both the viscosity of the oil product, which affected the transport of the PAC through the carrier, and the aromaticity, which affected the partition of PAC between the carrier and the skin. Literature data were analysed from mouse skin painting studies with mineral oils of known carcinogenicity. A linear relationship was shown between the amount of DNA adduct formation, expressed as alkylation frequency, and the arithmetic product of the total (3-6) ring PAC content and the BI, which we have termed the Carcinogenic Potency Index (CPI). Comparison of literature data on DNA alkylation frequencies for oil products and their carcinogenicity indicated that oils giving rise to an alkylation frequency below a certain threshold (ca. 1 adduct in 10(8) nucleotides) are non-carcinogenic to mouse skin. This threshold level can be translated into a value for the CPI, below which the genotoxic carcinogenic risk arising from skin contact with the oil product is considered to be negligible. The CPI for bitumens is well below this value, being both due to the low BI from bitumen, but more so, due to their low PAC content. For some bitumens diluted with solvents, i.e. cutback-bitumens, the CPI may exceed this value, indicating a possible carcinogenic risk

  20. Induction of skin carcinogenicity by alcohol and ultraviolet light.

    PubMed

    Saladi, R N; Nektalova, T; Fox, J L

    2010-01-01

    In western societies, casual consumption of alcohol during such outdoor activities as barbecuing and sunbathing is common. The current literature shows that alcohol drinkers have increased episodes of sunburn and a higher prevalence of skin cancer. Moreover, recent evidence suggests that the combination of subcarcinogenic (minimal) ultraviolet (UV) exposure with other behavioural, environmental and xenobiotic factors has resulted in increased incidents of skin-related health problems that also result in skin-cancer formation. We hypothesize that the combination of alcohol consumption with UV radiation can potentiate the skin carcinogenic effects through the intermediate biproducts or metabolites of alcohol, which serve as the photosensitizers, consequently enhancing the cellular damage. We have proposed a mechanism that explains the combined alcohol-UV radiation carcinogenicity and its potential involvement in enhancing skin damage in the multistep skin carcinogenesis process. Previous literature has explored this mutual effect but no studies have definitively ascribed the reasons for increased skin cancer prevalence among alcohol drinkers. Nevertheless, the preceding epidemiological data and clinical studies recognize this matter, making the further testing of this hypothesis necessary. PMID:19778305

  1. Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment.

    PubMed

    Feron, V J; Til, H P; de Vrijer, F; Woutersen, R A; Cassee, F R; van Bladeren, P J

    1991-01-01

    Aldehydes constitute a group of relatively reactive organic compounds. They occur as natural (flavoring) constituents in a wide variety of foods and food components, often in relatively small, but occasionally in very large concentrations, and are also widely used as food additives. Evidence of carcinogenic potential in experimental animals is convincing for formaldehyde and acetaldehyde, limited for crotonaldehyde, furfural and glycidaldehyde, doubtful for malondialdehyde, very weak for acrolein and absent for vanillin. Formaldehyde carcinogenesis is a high-dose phenomenon in which the cytotoxicity plays a crucial role. Cytotoxicity may also be of major importance in acetaldehyde carcinogenesis but further studies are needed to prove or disprove this assumption. For a large number of aldehydes (relevant) data on neither carcinogenicity nor genotoxicity are available. From epidemiological studies there is no convincing evidence of aldehyde exposure being related to cancer in humans. Overall assessment of the cancer risk of aldehydes in the diet leads to the conclusion that formaldehyde, acrolein, citral and vanillin are no dietary risk factors, and that the opposite may be true for acetaldehyde, crotonaldehyde and furfural. Malondialdehyde, glycidaldehyde, benzaldehyde, cinnamaldehyde and anisaldehyde cannot be evaluated on the basis of the available data. A series of aldehydes should be subjected to at least mutagenicity, cytogenicity and cytotoxicity tests. Priority setting for testing should be based on expected mechanism of action and degree of human exposure. PMID:2017217

  2. The Role of Alcohol as a Co-Carcinogen

    PubMed Central

    Cohen, Saul

    1979-01-01

    If cancer occurs because of what we eat, what we drink, what we smoke, and to some extent where we live and work, it follows that over 80% of cancers in human beings are related to environmental causes and therefore preventable. Since virtually every major chemical is under investigation for its carcinogenic effect, it is high time that the biological impact of alcohol received more than scant attention from the health professions as a lifestyle chemical which may be a factor in the commencement or promotion of modern man's most deadly disease. Clinical and epidemiological studies have implicated the excessive use of alcohol with the risk of developing certain cancers, especially when combined with heavy smoking. Other factors associated with drinking and increased risk of cancer consist of geographic, racial, sex and organ specificity, variations of which must be borne in mind in any study of potential environmental hazards. Research is currently under way to determine whether certain alcohol beverages may contain carcinogens, which may focus attention on the role of heavy drinking as one additional environmental factor in the spectrum of exogenous agents related to cancer production. PMID:21297757

  3. Comparative pulmonary carcinogenicity of inhaled beryllium A/J and C3H/HeJ mice

    SciTech Connect

    Nikula, K.J.; Belinsky, S.A.; Hoover, M.D.; Finch, G.L.

    1994-11-01

    The purpose of these investigations was to compare the pulomonary carcinogenicity of beryllium (Be) metal in A/J and C3H/HeJ mice, strains which are sensitive and resistant, respectively, to pulmonary neoplasia. Lesions in these mice will be used to study the molecular mechanisms of Be-induced carcinogenesis. Be, a metal that is generally negative in short-term genotoxicity assays, is a potent pulmonary carcinogen in F344/N rats. Although the epidemiological evidence is weak, Be is classified as a suspect human carcinogen.

  4. Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

    SciTech Connect

    Helguera, Aliuska Morales; Gonzalez, Maykel Perez . E-mail: mpgonzalez76@yahoo.es; Cordeiro, Maria Natalia D.S.; Perez, Miguel Angel Cabrera

    2007-06-01

    Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here - Quantitative Structure-Activity Relationship (QSAR) - are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions - expressed as fragment contributions to the carcinogenic activity - that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts for carcinogenicity predictions.

  5. Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen

    SciTech Connect

    Kurokawa, Y.; Maekawa, A.; Takahashi, M.; Hayashi, Y. )

    1990-07-01

    Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.111 references.

  6. [Mapping of carcinogens in the chemical production industry in the province of Ferrara].

    PubMed

    Maldotti, M; Spagnolo, M R; Minisci, S; De Rosa, E

    2008-01-01

    This study consists in the reconnaissance of the carcinogenic risk in some processing in Ferrara. The main object is to know, to estimate and to verify the diffusion of the carcinogenic substances and to estimate the number of the exposed or potentially exposed workers. The study has interested the synthesis chemistry and polymer production, woodworking, welding on stainless steel and chromium conversion coating and chrome electroplating. The research has involved 54 factories and 436 workers estimated exposed or potentially exposed to carcinogenic substances. The survey has consisted of inspections in the working places, collection of exposure data, control of the precautionary measures and exposure determination in the case of stainless steel welding. The smallest factories had less knowledge of the risk and for this reason it is necessary to keep constant attention. PMID:19344085

  7. Risk ranking priority of carcinogenic and/or genotoxic environmental contaminants in food in Belgium.

    PubMed

    Vromman, V; Maghuin-Rogister, G; Vleminckx, C; Saegerman, C; Pussemier, L; Huyghebaert, A

    2014-01-01

    This paper focuses on the risks of environmental carcinogenic and/or genotoxic contaminants in food. It describes, for each contaminant studied, the carcinogenicity and genotoxicity, the toxicological reference values, the exposure and the risk characterisation. The compounds studied were classified into 3 categories based on a risk assessment. Effects others than carcinogenicity and/or genotoxicity (e.g. endocrine disruption activity) were also taken into account for the classification. Given the low margin of exposure values for arsenic and lead, these two compounds are classified as priority 1 (high concern) for food safety and as a first priority to take actions to reduce exposure. Cadmium, methylmercury, dioxins and dioxin-like polychlorinated biphenyls (PCB), non-dioxin-like PCB and toxaphene are classified as priority 2 (medium concern). Polybrominated biphenyls, chlordane, heptachlor, dichlorodiphenyltrichloroethane (DDT) and metabolites, hexachlorobenzene, hexachlorocyclohexane (lindane included), polychlorophenols and their salts are classified as priority 3 (low concern). PMID:24471940

  8. Carcinogen assessment of coke oven emissions. Final report

    SciTech Connect

    Not Available

    1984-02-01

    Coke oven workers in Allegheny County, Pennsylvania and at 10 non-Allegheny County coke plants in the United States and Canada were found to be at an excess risk of mortality from cancer of all sites and from cancer of the lungs, bronchus, trachea, kidney, and prostate. An important finding of this study was the dose-response found by both length of exposure and intensity of exposure (top or side of the ovens) for mortality from cancer of the lungs, bronchus, and trachea. A study of Japanese coke oven workers also found them to be at an excess risk of lung cancer mortality. British studies of cancer mortality in coke oven workers have generally been negative, but there were weaknesses in these studies. Coke oven emissions produce positive results in mutagenicity studies. Coal tar, a condensate of coke oven emissions, and various constituents of coke oven emissions have been found to be positive in both mutagenicity and animal carcinogenicity studies.

  9. Carcinogenic PAH in waterpipe charcoal products

    PubMed Central

    Sepetdjian, Elizabeth; Saliba, Najat; Shihadeh, Alan

    2010-01-01

    Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafés. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content. PMID:20807559

  10. Carcinogenic PAH in waterpipe charcoal products.

    PubMed

    Sepetdjian, Elizabeth; Saliba, Najat; Shihadeh, Alan

    2010-11-01

    Because narghile waterpipe (shisha, hooka) smoking normally involves the use of burning charcoal, smoke inhaled by the user contains constituents originating from the charcoal in addition to those from the tobacco. We have previously found that charcoal accounts for most of the polyaromatic hydrocarbons (PAH) and carbon monoxide in the smoke of the waterpipe, both of which are present in alarming quantities. Because charcoal manufacturing conditions favor formation of PAH, it is reasonable to assume that charcoal sold off the shelf may be contaminated by PAH residues. These residues may constitute a significant fraction of the PAH inhaled by the waterpipe user and those in her/his vicinity. We measured PAH residues on three kinds of raw waterpipe charcoal sampled from Beirut stores and cafés. We found that PAH residues in raw charcoal can account for more than half of the total PAH emitted in the mainstream and sidestream smoke, and about one sixth of the carcinogenic 5- and 6-ring PAH compounds. Total PAH content of the three charcoal types varied systematically by a factor of six from the charcoal with the least to the greatest PAH residue. These findings indicate the possibility of regulating charcoal carcinogen content. PMID:20807559

  11. Evidence supporting product standards for carcinogens in smokeless tobacco products

    PubMed Central

    Hatsukami, Dorothy K.; Stepanov, Irina; Severson, Herb; Jensen, Joni A.; Lindgren, Bruce R.; Horn, Kimberly; Khariwala, Samir S.; Martin, Julia; Carmella, Steven G.; Murphy, Sharon E.; Hecht, Stephen S.

    2014-01-01

    Smokeless tobacco (ST) products sold in the U.S. vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of ST use versus constituent levels in the ST product in exposure of users to carcinogens. In this study, ST users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and ST use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, ST users recorded the amount and duration of ST use on a daily basis using their diary cards. Results showed that independent of pattern of ST use and nicotine yields, levels of TSNA in ST products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in ST products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. PMID:25524878

  12. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.

    PubMed

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

    The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically important liver fluke species belonging to the family Opisthorchiidae and the major agent causing opisthorchiasis over a vast territory, covering Russia, Kazakhstan and several European countries. The similarity between the diseases caused by O. felineus and other liver flukes, O. viverrini and Clonorchis sinensis, in clinical manifestations and course suggests that the scenarios of their development and, possibly, complications have much in common. The International Agency for Research on Cancer classified O. viverrini and C. sinensis as group 1 agents and the major factors inducing cholangiocarcinoma in endemic regions. However, a carcinogenic potential of O. felineus is poorly studied. This review characterizes O. felineus, briefs the epidemiological situation in Western Siberia, the world's largest opisthorchiasis focus, and assesses the carcinogenic potential of this liver fluke. The review is based on a comprehensive analysis of the published medical data on opisthorchiasis and its complications in Western Siberia. Results of performed analysis reflect the actual epidemiological situation in opisthorchiasis focus and suggest an association of this disease with bile duct cancer. PMID:26740360

  13. The role of pancreatic islets in experimental pancreatic carcinogenicity.

    PubMed Central

    Ishikawa, O.; Ohigashi, H.; Imaoka, S.; Nakai, I.; Mitsuo, M.; Weide, L.; Pour, P. M.

    1995-01-01

    Our previous studies have suggested that the presence of intact islets is essential for the induction of pancreatic exocrine tumors in the Syrian hamster model. To validate this, we investigated the effect of the carcinogen, N-nitrosobis(2-oxo-propyl)amine (BOP) in hamsters, in which homologous isolated intact islets were transplanted into the submandibular gland (SMG). Freshly isolated pure islets from hamster donors were transplanted into the left SMG of 20 female host hamsters. Ten of these hamsters (group 1) received BOP (40 mg/kg) weekly for 3 weeks. Another 10 hamsters (group 2) were kept untreated. In groups 3 and 4 (10 hamsters each) the salt solution or isolated pancreatic ductal cells, respectively, was injected into the gland. In other groups (10 hamsters each) islets were transplanted into the peri-SMG connective tissue (group 5) or into the renal subcapsular space (group 6). Hamsters of group 1 (40 mg/kg, weekly for 3 weeks) as were group 7 hamsters, which served as BOP-treated controls. All BOP-treated hamsters developed pancreatic lesions. Similar hyperplastic and atypical ductal/ductular proliferation and in situ carcinoma were found in the SMG of many group 1 hamsters. No such lesions were found in the SMG, peri-SMG, or renal subcapsular space of the other groups. Islets appear to be involved in carcinogenicity of BOP. The mechanism is obscure. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:7485408

  14. Systems biology perspectives on the carcinogenic potential of radiation

    PubMed Central

    Barcellos-Hoff, Mary Helen; Adams, Cassandra; Balmain, Allan; Costes, Sylvain V.; Demaria, Sandra; Illa-Bochaca, Irineu; Mao, Jian Hua; Ouyang, Haoxu; Sebastiano, Christopher; Tang, Jonathan

    2014-01-01

    This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood non-targeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment.

  15. Target organs in chronic bioassays of 533 chemical carcinogens

    SciTech Connect

    Gold, L.S.; Slone, T.H.; Manley, N.B. ); Bernstein, L. )

    1991-06-01

    A compendium of carcinogenesis bioassay results organized by target organ is presented for 533 chemicals that are carcinogenic in at least one species. This compendium is based primarily on experiments in rats or mice; results in hamsters, nonhuman primates, and dogs are also reported. The compendium can be used to identify chemicals that induce tumors at particular sites, and to determine whether target sites are the same for chemicals positive in more than one species. The Carcinogenic Potency Database (CPDB), which includes results of 3969 experiments, is used in the analysis. The published CPDB includes details on each test, and literature references. Chemical carcinogens are reported for 35 different target organs in rats or mice. More than 80% of the carcinogens in each of these species are positive in at least one of the 8 most frequent target sites; liver, lung, mammary gland, stomach, vascular system, kidney, hematopoietic system, and urinary bladder. An analysis is presented of how well one can predict the carcinogenic response in mice from results in rats, or vice versa. Among chemicals tested in both species, 76% of rat carcinogens are positive in mice, and 71% of mouse carcinogens are positive in rats. Prediction is less accurate to the same target site: 52% of rat carcinogens are positive in the same site in mice, and 48% of mouse carcinogens are positive in the same site in rats. The liver is the most frequent site in common between rats and mice.

  16. Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments.

    PubMed Central

    Gottmann, E; Kramer, S; Pfahringer, B; Helma, C

    2001-01-01

    We compared 121 replicate rodent carcinogenicity assays from the two parts (National Cancer Institute/National Toxicology Program and literature) of the Carcinogenic Potency Database (CPDB) to estimate the reliability of these experiments. We estimated a concordance of 57% between the overall rodent carcinogenicity classifications from both sources. This value did not improve substantially when additional biologic information (species, sex, strain, target organs) was considered. These results indicate that rodent carcinogenicity assays are much less reproducible than previously expected, an effect that should be considered in the development of structure-activity relationship models and the risk assessment process. PMID:11401763

  17. Target organs in chronic bioassays of 533 chemical carcinogens.

    PubMed Central

    Gold, L S; Slone, T H; Manley, N B; Bernstein, L

    1991-01-01

    A compendium of carcinogenesis bioassay results organized by target organ is presented for 533 chemicals that are carcinogenic in at least one species. This compendium is based primarily on experiments in rats or mice; results in hamsters, nonhuman primates, and dogs are also reported. The compendium can be used to identify chemicals that induce tumors at particular sites, and to determine whether target sites are the same for chemicals positive in more than one species. The Carcinogenic Potency Database (CPDB), which includes results of 3969 experiments, is used in the analysis. The published CPDB includes details on each test, and literature references. Chemical carcinogens are reported for 35 different target organs in rats or mice. More than 80% of the carcinogens in each of these species are positive in at least one of the 8 most frequent target sites: liver, lung, mammary gland, stomach, vascular system, kidney, hematopoietic system, and urinary bladder. An analysis is presented of how well one can predict the carcinogenic response in mice from results in rats, or vice versa. Among chemicals tested in both species, 76% of rat carcinogens are positive in mice, and 71% of mouse carcinogens are positive in rats. Prediction is less accurate to the same target site: 52% of rat carcinogens are positive in the same site in mice, and 48% of mouse carcinogens are positive in the same site in rats. The liver is the most frequent site in common between rats and mice. PMID:1773795

  18. Molecular fingerprints of environmental carcinogens in human cancer.

    PubMed

    Ceccaroli, C; Pulliero, A; Geretto, M; Izzotti, A

    2015-01-01

    Identification of specific molecular changes (fingerprints) is important to identify cancer etiology. Exploitable biomarkers are related to DNA, epigenetics, and proteins. DNA adducts are the turning point between environmental exposures and biological damage. DNA mutational fingerprints are induced by carcinogens in tumor suppressor and oncogenes. In an epigenetic domain, methylation changes occurs in specific genes for arsenic, benzene, chromium, and cigarette smoke. Alteration of specific microRNA has been reported for environmental carcinogens. Benzo(a)pyrene, cadmium, coal, and wood dust hits specific heat-shock proteins and metalloproteases. The multiple analysis of these biomarkers provides information on the carcinogenic mechanisms activated by exposure to environmental carcinogens. PMID:26023758

  19. Hepatic metabolism of carcinogenic β-asarone.

    PubMed

    Cartus, Alexander T; Stegmüller, Simone; Simson, Nadine; Wahl, Andrea; Neef, Sylvia; Kelm, Harald; Schrenk, Dieter

    2015-09-21

    β-Asarone (1) belongs to the group of naturally occurring phenylpropenes like eugenol or anethole. Compound 1 is found in several plants, e.g., Acorus calamus or Asarum europaeum. Compound 1-containing plant materials and essential oils thereof are used to flavor foods and alcoholic beverages and as ingredients of many drugs in traditional phytomedicines. Although 1 has been claimed to have several positive pharmacological effects, it was found to be genotoxic and carcinogenic in rodents (liver and small intestine). The mechanism of action of carcinogenic allylic phenylpropenes consists of the metabolic activation via cytochrome P450 enzymes and sulfotransferases. In vivo experiments suggested that this pathway does not play a major role in the carcinogenicity of the propenylic compound 1 as is the case for other propenylic compounds, e.g., anethole. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rats, bovines, porcines, and humans using (1)H NMR, HPLC-DAD, and LC-ESI-MS/MS techniques. We synthesized the majority of identified metabolites which were used as reference compounds for the quantification and final verification of metabolites. Microsomal epoxidation of the side chain of 1 presumably yielded (Z)-asarone-1',2'-epoxide (8a) which instantly was hydrolyzed to the corresponding erythro- and threo-configurated diols (9b, 9a) and the ketone 2,4,5-trimethoxyphenylacetone (13). This was the main metabolic pathway in the metabolism of 1 in all investigated liver microsomes. Hydroxylation of the side chain of 1 led to the formation of three alcohols at total yields of less than 30%: 1'-hydroxyasarone (2), (E)- and (Z)-3'-hydroxyasarone (4 and 6), with 6 being the mainly formed alcohol and 2 being detectable only in liver microsomes of Aroclor 1254-pretreated rats. Small amounts of 4 and 6 were further oxidized to the corresponding carbonyl

  20. Assessing the potential carcinogenic activity of magnetic fields using animal models.

    PubMed Central

    McCann, J; Kavet, R; Rafferty, C N

    2000-01-01

    We update our 1997 publication by reviewing 29 new reports of tests of magnetic fields (MFs) in six different in vivo animal models of carcinogenesis: 2-year, lifetime, or multigeneration exposure studies in rats or mice; and promotion/progression models (rat mammary carcinoma, rat liver focus, mouse skin, several models of human leukemia/lymphoma in rats and mice, and brain cancer in rats). Individual experiments are evaluated using a set of data quality criteria, and summary judgments are made across multiple experiments by applying a criterion of rough reproducibility. The potential for carcinogenicity of MFs is discussed in light of the significant body of carcinogenesis data from animal bioassays that now exists. Excluding abstracts, approximately 80% of the 41 completed studies identified in this and our previous review roughly satisfy data quality criteria. Among these studies, the criterion for independent reproducibility is not satisfied for any positive results but is satisfied for negative results in chronic bioassays in rats and mice and for negative results in both promotion and co-promotion assays using the SENCAR mouse skin model. Results of independent replication studies using the rat mammary carcinoma model were conflicting. We conclude that long-term exposure to continuous 50- or 60-Hz MFs in the range of 0.002-5 mT is unlikely to result in carcinogenesis in rats or mice. Though results of most promotion/progression assays are negative, a weak promoting effect of MFs under certain exposure conditions cannot be ruled out based on available data. PMID:10698725

  1. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    PubMed

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. PMID:24727049

  2. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

    PubMed

    Yılmaz, Serkan; Uçar, Aslı

    2014-12-01

    The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180-200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specify the adverse effects of aspartame. Therefore, we aimed to review the oldest to latest works published in major indices to gather information within this article. With respect to published data, genotoxicity and carcinogenicity of aspartame is still confusing. So, consumers should be aware of the potential side effects of aspartame before they consume it. PMID:24510317

  3. Modulation of carcinogen bioavailability by immunisation with benzo[a]pyrene-conjugate vaccines.

    PubMed

    Grova, Nathalie; Prodhomme, Emmanuel J F; Schellenberger, Mario T; Farinelle, Sophie; Muller, Claude P

    2009-06-24

    Benzo[a]pyrene (B[a]P) conjugate vaccines based on ovalbumin, tetanus toxoid and diphtheria toxoid (DT) as carrier proteins were developed to investigate the effect of specific antibodies on the bioavailability of this ubiquitous carcinogen and its metabolites. After metabolic activation of this prototype carcinogen, B[a]P forms DNA adducts which initiate chemical carcinogenesis. B[a]P-DT conjugate induced the most robust immune response. The antibodies reacted not only with B[a]P but also with the proximate carcinogen 7,8-diol-B[a]P. Antibodies modulated the bioavailability of B[a]P and its metabolic activation in a dose-dependent manner by sequestration in the blood. Our results showed that this immune prophylactic strategy influences the pharmacokinetic of B[a]P and further studies to investigate their effects on chemical carcinogenesis are warranted. PMID:19406187

  4. An evaluation of 6 short-term tests for detecting organic chemical carcinogens.

    PubMed Central

    Purchase, I. F.; Longstaff, E.; Ashby, J.; Styles, J. A.; Anderson, D.; Lefevre, P. A.; Westwood, F. R.

    1978-01-01

    A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint. This study compared the performance of 6 such tests on a selection of 120 organic chemicals. The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant. A further 4 tests were examined briefly, but were not included in the complete evaluation. The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes. There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively). These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others. Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone. The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved. All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test. Structural analogy may have a part to play in the rapid detection of environmental carcinogens, and some general guidelines for its use are given. PMID:354672

  5. Rapid fast-mapping abilities in 2-year-olds.

    PubMed

    Spiegel, Chad; Halberda, Justin

    2011-05-01

    Learning a new word consists of two primary tasks that have often been conflated into a single process: referent selection, in which a child must determine the correct referent of a novel label, and referent retention, which is the ability to store this newly formed label-object mapping in memory for later use. In addition, children must be capable of performing these tasks rapidly and repeatedly as they are frequently exposed to novel words during the course of natural conversation. Here we used a preferential pointing task to investigate 2-year-olds' (N=72) ability to infer the referent of a novel noun from a single ambiguous exposure and their ability to retain this mapping over time. Children were asked to identify the referent of a novel label on six critical trials distributed throughout the course of a 10-min study involving many familiar and novel objects. On these critical trials, images of a known object and a novel object (e.g., a ball and a nameless artifact constructed in the laboratory) appeared on two computer screens and a voice asked children to "point at the _____ [e.g., glark]." Following label onset, children were allowed only 3s during which to infer the correct referent, point at it, and potentially store this new word-object mapping. In a final posttest trial, all previously labeled novel objects appeared and children were asked to point to one of them (e.g., "Can you find the glark?"). To succeed, children needed to have initially mapped the novel labels correctly and retained these mappings over the course of the study. Despite the difficult demands of the current task, children successfully identified the target object on the retention trial. We conclude that 2-year-olds are able to fast map novel nouns during a brief single exposure under ambiguous labeling conditions. PMID:21145067

  6. 78 FR 4419 - Draft Report on Carcinogens Monographs for 1-Bromopropane and Cumene; Availability of Documents...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-22

    ...: Cancer studies that support the listing-- including those in humans, animals, and studies on possible... HUMAN SERVICES National Institutes of Health Draft Report on Carcinogens Monographs for 1-Bromopropane... prepares the RoC on behalf of the Secretary of Health and Human Services. The NTP follows an...

  7. Medical Care and Your 1- to 2-Year-Old

    MedlinePlus

    ... Zika & Pregnancy Medical Care and Your 1- to 2-Year-Old KidsHealth > For Parents > Medical Care and Your 1- to 2-Year-Old Print A A A Text Size ... Following simple instructions? Saying a few words? Combining two words by age 2? The doctor may ask ...

  8. Carcinogenicity of beryllium hydroxide and alloys

    SciTech Connect

    Groth, D.H.; Kommineni, C.; Mackay, G.R.

    1980-02-01

    Animal experiments are presented which show that Be metal, BeAl alloy, passivated Be metal, and beryllium hydroxide are pulmonary carcinogens in rats. These findings are supported by successful transplantation experiments. In addition, other alloys of Be, VBe/sub 12/, TiBe/sub 12/, TaBe/sub 12/, NbBe/sub 12/, Be/sub 2/B, and Be/sub 4/B were found to produce pulmonary metaplasia, frequently a preneoplastic lesion in rats. Old rats are shown to be more susceptible to the induction of pulmonary metaplasia than young adult rats. These results indicate that a lower dose of Be would be required to produce cancer in old animals compared to young adult animals. A discussion on the lung cancer incidence in beryllium production workers is presented.

  9. Delineation of a Carcinogenic Helicobacter pylori Proteome*

    PubMed Central

    Franco, Aime T.; Friedman, David B.; Nagy, Toni A.; Romero-Gallo, Judith; Krishna, Uma; Kendall, Amy; Israel, Dawn A.; Tegtmeyer, Nicole; Washington, M. Kay; Peek, Richard M.

    2009-01-01

    Helicobacter pylori is the strongest known risk factor for gastric adenocarcinoma, yet only a fraction of infected persons ever develop cancer. The extensive genetic diversity inherent to this pathogen has precluded comprehensive analyses of constituents that mediate carcinogenesis. We previously reported that in vivo adaptation of a non-carcinogenic H. pylori strain endowed the output derivative with the ability to induce adenocarcinoma, providing a unique opportunity to identify proteins selectively expressed by an oncogenic H. pylori strain. Using a global proteomics DIGE/MS approach, a novel missense mutation of the flagellar protein FlaA was identified that affects structure and function of this virulence-related organelle. Among 25 additional differentially abundant proteins, this approach also identified new proteins previously unassociated with gastric cancer, generating a profile of H. pylori proteins to use in vaccine development and for screening persons infected with strains most likely to induce severe disease. PMID:19470446

  10. Carcinogenicity of consumption of red and processed meat: What about environmental contaminants?

    PubMed

    Domingo, José L; Nadal, Martí

    2016-02-01

    In October 26, 2015, the International Agency for Research on Cancer (IARC) issued a press release informing of the recent evaluation of the carcinogenicity of red and processed meat consumption. The consumption of red meat and processed meat was classified as "probably carcinogenic to humans", and as "carcinogenic to humans", respectively. The substances responsible of this potential carcinogenicity would be generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures (N-nitroso-compounds, polycyclic aromatic hydrocarbons and heterocyclic aromatic amines). However, in its assessments, the IARC did not make any reference to the role that may pose some carcinogenic environmental pollutants, which are already present in raw or unprocessed meat. The potential role of a number of environmental chemical contaminants (toxic trace elements, polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, polychlorinated diphenyl ethers, polychlorinated naphthalenes and perfluoroalkyl substances) on the carcinogenicity of consumption of meat and meat products is discussed in this paper. A case-study, Catalonia (Spain), is specifically assessed, while the influence of cooking on the concentrations of environmental pollutants is also reviewed. It is concluded that although certain cooking processes could modify the levels of chemical contaminants in food, the influence of cooking on the pollutant concentrations depends not only on the particular cooking process, but even more on their original contents in each specific food item. As most of these environmental pollutants are organic, cooking procedures that release or remove fat from the meat should tend to reduce the total concentrations of these contaminants in the cooked meat. PMID:26656511

  11. Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens.

    PubMed Central

    Elcombe, Clifford R; Odum, Jenny; Foster, John R; Stone, Susan; Hasmall, Susan; Soames, Anthony R; Kimber, Ian; Ashby, John

    2002-01-01

    We studied nine presumed nongenotoxic rodent carcinogens, as defined by the U.S. National Toxicology Program (NTP), to determine their ability to induce acute or subacute biochemical and tissue changes that may act as useful predictors of nongenotoxic rodent carcinogenesis. The chemicals selected included six liver carcinogens (two of which are peroxisome proliferators), three thyroid gland carcinogens, and four kidney carcinogens. We administered the chemicals (diethylhexyl phthalate, cinnamyl anthranilate, chlorendic acid, 1,4-dichlorobenzene, monuron, ethylene thiourea, diethyl thiourea, trimethyl thiourea, and d-limonene to the same strains of mice and rats used in the original NTP bioassays (nine chemicals to rats and seven to mice). Selected tissues (liver, thyroid gland, and kidney) were collected from groups of animals at 7, 28, and 90 days for evaluation. Tissue changes selected for study were monitored for all of the test groups, irrespective of the specificity of the carcinogenic responses observed in those tissues. This allowed us to assess both the carcinogen specificity and the carcinogen sensitivity of the events being monitored. We studied relative weight, cell labeling indices, and pathologic changes such as hypertrophy in all tissues; a range of cytochrome P450 enzymes and palmitoyl coenzyme A oxidase in the liver; changes in the levels of plasma total triiodothyronine, total thyroxine, and thyroid-stimulating hormone (TSH) as markers of thyroid gland function; and hyaline droplet formation, tubular basophilia, and the formation of granular casts in the kidney. There were no single measurements that alerted specifically to the carcinogenicity of the agents to the rodent liver, thyroid gland, or kidney. However, in the majority of cases, the chemical induction of cancer in a tissue was preceded by a range of biochemical/morphologic changes, most of which were moderately specific for a carcinogenic outcome, and some of which were highly specific for

  12. Efficacy and safety of dutasteride, tamsulosin and their combination in a subpopulation of the CombAT study: 2-year results in Asian men with moderate-to-severe BPH.

    PubMed

    Chung, B-H; Roehrborn, C G; Siami, P; Major-Walker, K; Morrill, B B; Wilson, T H; Montorsi, F

    2009-01-01

    Although ethnicity-based differences in prostate size and physiology have been reported, results of benign prostatic hyperplasia (BPH) treatment trials in predominantly Caucasian patients are assumed to be applicable to non-Caucasian populations. This post hoc analysis investigated whether an Asian subpopulation of men with moderate-to-severe BPH in the CombAT study achieves treatment responses in line with those of the overall study population. In this double-blind, randomized, parallel-group trial, 325 Asian men were assigned to treatment with 0.5 mg dutasteride once daily, 0.4 mg tamsulosin once daily or the combination. Decrease in international prostate symptom score (IPSS) at month 24 from baseline (the primary endpoint) was significantly greater with combination treatment compared with tamsulosin (P<0.05), and numerically, but not statistically significantly, greater compared with dutasteride. Mean IPSS was reduced from baseline by 7.5 (+/-0.84) in the combination group, by 6.3 (+/-0.86) in the dutasteride group and by 4.5 (+/-0.78) in the tamsulosin group, resulting in respective mean IPSS at months 24 of 11.4 (+/-0.60), 12.7 (+/-0.70) and 14.3 (+/-0.74). The adverse event profile was similar to that observed in the overall CombAT population, and drug-related adverse events were more common with combination therapy (26%) than with tamsulosin (15%) or dutasteride (9%). No unexpected adverse events emerged. In conclusion, in Asian men with moderate-to-severe lower urinary tract symptoms and an enlarged prostate, combination therapy achieved significantly greater improvements from baseline BPH symptoms, flow rate, quality of life, reduced prostate volume and improved treatment satisfaction compared with tamsulosin monotherapy. PMID:18813219

  13. Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study

    PubMed Central

    Cordonnier, Catherine; Ljungman, Per; Juergens, Christine; Maertens, Johan; Selleslag, Dominik; Sundaraiyer, Vani; Giardina, Peter C.; Clarke, Keri; Gruber, William C.; Scott, Daniel A.; Schmoele-Thoma, Beate

    2015-01-01

    Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention. Methods. In an open-label study, patients (n = 251) 3–6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed. Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99–23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00–6.97), and little change after PPSV23 (GMFR range, 0.86–1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines. Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable. Clinical Trials Registration. NCT00980655. PMID:25870329

  14. 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 6 2012-07-01 2012-07-01 false 13 Carcinogens (4-Nitrobiphenyl, etc.). 1910.1003 Section 1910.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) OCCUPATIONAL SAFETY AND HEALTH STANDARDS (CONTINUED) Toxic and Hazardous Substances § 1910.1003 13 Carcinogens...

  15. 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... representatives, and the Assistant Secretary in accordance with 29 CFR 1910.1020 (a) through (e) and (g) through... impervious to the passage of the material and would prevent the entry of the carcinogen addressed by this... Carcinogens: (A) 4-Nitrobiphenyl: Cancer. (B) alpha-Naphthylamine: Cancer; skin irritation; and acute...

  16. Carcinogens in the Workplace: A Scientific, Political and Social Problem

    PubMed Central

    Atherley, Gordon; Whiting, Robert

    1982-01-01

    Investigation, assessment, and management of carcinogenic risks are not only scientific but also political responsibilities. In Canada, this becomes cumbersome, since local, provincial and federal policies are involved. The process also involves workers and management. This article outlines Canadian legislative experience, the principles involved, the methods of risk assessment, and the classification of carcinogens in the workplace. PMID:21286078

  17. Workshop on problem areas associated with developing carcinogen guidelines

    SciTech Connect

    Not Available

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  18. [The carcinogenic and anticarcinogenic properties of neozon D].

    PubMed

    Pliss, G B; Vlasov, N N; Zabezhinskiĭ, M A

    1991-01-01

    Continuous administration of neozone D to dogs and rats failed to reveal its carcinogenicity. Nor did the agent potentiate the carcinogenic effect of 2-naphthylamine and benzidine in rats. Conversely, neozone D was found to inhibit benzidine-induced carcinogenesis in female rats. PMID:2014680

  19. Method for converting asbestos to non-carcinogenic compounds

    DOEpatents

    Selby, Thomas W.

    1996-01-01

    Hazardous and carcinogenic asbestos waste characterized by a crystalline fibrous structure is transformed into non-carcinogenic, relatively nonhazardous, and non-crystalline solid compounds and gaseous compounds which have commercial utilization. The asbestos waste is so transformed by the complete fluorination of the crystalline fibrous silicate mineral defining the asbestos.

  20. Method for converting asbestos to non-carcinogenic compounds

    DOEpatents

    Selby, T.W.

    1996-08-06

    Hazardous and carcinogenic asbestos waste characterized by a crystalline fibrous structure is transformed into non-carcinogenic, relatively nonhazardous, and non-crystalline solid compounds and gaseous compounds which have commercial utilization. The asbestos waste is so transformed by the complete fluorination of the crystalline fibrous silicate mineral defining the asbestos. 7 figs.

  1. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  2. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    EPA Science Inventory

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  3. Multicomponent criteria for predicting carcinogenicity: dataset of 30 NTP chemicals.

    PubMed Central

    Huff, J; Weisburger, E; Fung, V A

    1996-01-01

    This article is in response to the challenge issued to the scientific community by the National Toxicology Program to predict the carcinogenicity potential of 30 chemicals previously selected for long-term carcinogenicity testing. Utilizing the available toxicologic, genetic, and structural information on 30 chemicals previously selected for long-term carcinogenicity testing, we predict that 16 chemicals (53%) would induce some indication of carcinogenic activity in rodents; we further predict that 10 chemicals (33%) would be associated with weak or equivocal carcinogenic responses, and another 4 (13%) would give no indication of carcinogenicity. Our level of certainty is indicated for many of these predictions. Nonetheless, we believe that most instances of guessing whether a chemical would eventually induce cancer in experimental animals and hence represent a carcinogenic hazard to humans are fraught with considerable uncertainty: uncertainty that can only be relieved by long-term testing for carcinogenicity in animals or by conducting an epidemiologic investigation of exposed individuals or groups. We further believe that the day may come when our predictive acumen will be upgraded to such an extent that we might eventually obviate cancer testing. Until then, and in the best interests of public health, however, we urge long term testing of chemicals in animals be continued, at increased pace. PMID:8933061

  4. LABORATORY EVALUATION OF MARINE FISHES AS CARCINOGEN ASSAY SUBJECTS

    EPA Science Inventory

    The U.S. Environmental Protection Agency (EPA) and the National Cancer Inst. (NCI) have major responsibilities for determining the fate and risks of carcinogenic agents in the natural environment. Under the auspices of EPA/NCI, the Carcinogen Research Team at the USEPA Lab, Gulf ...

  5. GENE-TOX CARCINOGEN DATA BASE: CONSTRUCTION, DESCRIPTION, AND ANALYSIS

    EPA Science Inventory

    The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indi...

  6. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol.

    PubMed

    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi; Igarashi, Maki; Nakae, Dai

    2008-08-01

    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. PMID:18350280

  7. Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.

    PubMed Central

    Kurokawa, Y; Maekawa, A; Takahashi, M; Hayashi, Y

    1990-01-01

    Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes. Images FIGURE 1. FIGURE 2. FIGURE 5. FIGURE 6. FIGURE 7. FIGURE 8. FIGURE 9. FIGURE 10. FIGURE 11. FIGURE 12. PMID:2269236

  8. Estrogenic status modulates aryl hydrocarbon receptor - mediated hepatic gene expression and carcinogenicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Estrogenic status is thought to influence the cancer risk in women and has been reported to affect toxicity of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in animals. The objective of this study was to examine the influence of estradiol (E2) on hepatic gene expression changes mediated by 7,...

  9. STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) AMONG MUTAGENS AND CARCINOGENS: A REVIEW

    EPA Science Inventory

    The review is an introduction to methods for evaluating structure-activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correla...

  10. On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

    PubMed

    Ilnitsky, A P; Belitsky, G A; Shabad, L M

    1976-05-01

    The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment. PMID:1016954

  11. PREDICTING RODENT CARCINOGENICITY OF AMES TEST "FALSE POSITIVES" BY IN VIVO BIOCHEMICAL PARAMETERS

    EPA Science Inventory

    Twenty-eight chemicals known to be mutagenic in the Ames test but not carcinogenic in rodent bioassays were selected for study. The effects of these chemicals on four biochemical assays (hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), ...

  12. Insights into the carcinogenic mode of action of arsenic

    SciTech Connect

    Kligerman, A.D. Tennant, A.H.

    2007-08-01

    That arsenic can induce cancer in humans has been known since the late 17th century, yet how arsenic induces cancer has been the subject of numerous scientific publications. Various modes of action (MOA) have been proposed for arsenic's carcinogenicity. In this paper we review our previous studies on the ability of arsenicals to cause DNA damage, the relative inability of these arsenicals to induce point mutations, and the involvement of arsenicals in spindle disruption. We present new evidence that shows that reduced glutathione (GSH) can chemically reduce inactive pentavalent arsenicals to trivalent arsenicals which can disrupt tubulin polymerization, and show that reactive oxygen species (ROS) are most likely not involved in tubulin disruption. A hypothesis is also presented on how arsenic may induce stable chromosome aberrations (CAs) that can lead to cancer, thus supporting a role for genetic damage in the MOA for arsenic. We then propose promising areas of research that might give insight into the MOA of arsenic.

  13. [Comparative carcinogenic properties of basalt fiber and chrysotile-asbestos].

    PubMed

    Nikitina, O V; Kogan, F M; Vanchugova, N N; Frash, V N

    1989-01-01

    In order to eliminate asbestos adverse effect on workers' health it was necessary to use mineral rayon, primarily basalt fibre, instead of asbestos. During a chronic experiment on animals the oncogenicity of 2 kinds of basalt fibre was studied compared to chrysotile asbestos. The dust dose of 25 mg was twice administered by intraperitonial route. All types of dust induced the onset of intraperitonial mesotheliomas but neoplasm rates were significantly lower in the groups exposed to basalt fibre. There was no credible data on the differences between the groups exposed to various types of basalt fibre. Since the latter produced some oncogenic effect, it was necessary to develop a complex of antidust measures, fully corresponding to the measures adopted for carcinogenic dusts. PMID:2545547

  14. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    SciTech Connect

    Valerio, Luis G. . E-mail: luis.valerio@FDA.HHS.gov; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

    2007-07-01

    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  15. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    PubMed

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  16. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

    PubMed Central

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  17. Patterns of fatigue and its correlates over the first 2 years after traumatic brain injury.

    PubMed

    Bushnik, Tamara; Englander, Jeffrey; Wright, Jerry

    2008-01-01

    This study used a prospective longitudinal design to quantify fatigue and associated factors during the first 2 years after traumatic brain injury (TBI). Fifty-one individuals were assessed at 3 time points: within the first 6, 12, and 18-24 months after TBI. Self-reported fatigue improved during the first year, as did pain, sleep quality, cognitive independence, and involvement in productive activity. Further changes up to 2 years after TBI were not observed. The subset of individuals who reported significant increases in fatigue over the first 2 years demonstrated poorer outcomes in cognition, motor symptoms, and general functioning than those with decreased or stable fatigue. PMID:18219232

  18. Evaluation of the potential carcinogenicity of cadmium, cadium acetate, cadmium bromide, cadmium chloride. Final report

    SciTech Connect

    Not Available

    1988-06-01

    Cadmium is a probable human carcinogen, classified as weight-of-evidence Group B1 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). Evidence on potential carcinogenicity from animal studies is Sufficient, and the evidence from human studies is Limited. The potency factor (F) for cadmium is estimated to be 57.9/(mg/kg/day) (based on epidemiology data for cadmium workers), placing it in potency group 2 according to the CAG's methodology for evaluating potential carcinogens (U.S. EPA, 1986b). Cadmium weight of evidence and potency are based on epidemiology data for cadmium workers exposed to cadmium oxide and/or cadmium fume. Although human data for cadmium salts are lacking, due to the responsiveness of animals to soluble cadmium compounds, especially cadmium chloride, the weight of evidence and potency for cadmium acetate, cadmium bromide and cadmium chloride are considered to be the same as those cadmium compounds to which workers are exposed. Thus, cadmium acetate, cadmium bromide, and cadmium chloride are all classified as weight-of-evidence Group and the potency group, cadmium, cadmium acetate, cadmium bromide, and cadmium chloride are assigned MEDIUM hazard rankings for the purposes of RQ adjustment. Combining the weight-of-evidence group and the potency group, carbon tetrachloride is assigned a MEDIUM hazard ranking for the purposes of RQ adjustment.

  19. Nicotine and carcinogen exposure after water pipe smoking in hookah bars

    PubMed Central

    St.Helen, Gideon; Benowitz, Neal L; Dains, Katherine M; Havel, Christopher; Peng, Margaret; Jacob, Peyton

    2014-01-01

    Background Water pipe tobacco smoking is spreading globally and is increasingly becoming popular in the United States, particularly among young people. While many perceive water pipe smoking to be relatively safe, clinical experimental studies indicate significant exposures to tobacco smoke carcinogens following water pipe use. We investigated biomarkers of nicotine intake and carcinogen exposure from water pipe smoking in the naturalistic setting of hookah bars. Methods Fifty-five experienced water pipe users were studied before and after smoking water pipe in their customary way in a hookah bar. Urine samples were analyzed for nicotine, cotinine, the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (NNAL), and mercapturic acid metabolites of volatile organic compounds (VOCs). Results We found an average 73-fold increase in nicotine, 4-fold increase in cotinine, 2-fold increase in NNAL, and 14-91% increase in VOC mercapturic acid metabolites immediately following water pipe smoking. We saw moderate to high correlations between changes in tobacco-specific biomarkers (nicotine, cotinine, and NNAL) and several mercapturic acid metabolites of VOC. Conclusion Water pipe smoking in a hookah bar is associated with significant nicotine intake and carcinogen exposure. Impact Given the significant intake of nicotine and carcinogens, chronic water pipe use could place users at increased risk of cancer and other chronic diseases. PMID:24836469

  20. Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles

    PubMed Central

    MAGAYE, RUTH; ZHAO, JINSHUN; BOWMAN, LINDA; DING, MIN

    2012-01-01

    The nanotechnology industry has matured and expanded at a rapid pace in the last decade, leading to the research and development of nanomaterials with enormous potential. The largest source of these nanomaterials is the transitional metals. It has been revealed that numerous properties of these nano-sized elements are not present in their bulk states. The nano size of these particles means they are easily transported into biological systems, thus, raising the question of their effects on the susceptible systems. Although advances have been made and insights have been gained on the effect of transitional metals on susceptible biological systems, there still is much ground to be covered, particularly with respect to our knowledge on the genotoxic and carcinogenic effects. Therefore, this review intends to summarize the current knowledge on the genotoxic and carcinogenic potential of cobalt-, nickel- and copper-based nanoparticles indicated in in vitro and in vivo mammalian studies. In the present review, we briefly state the sources, use and exposure routes of these nanoparticles and summarize the current literature findings on their in vivo and in vitro genotoxic and carcinogenic effects. Due to the increasing evidence of their role in carcinogenicity, we have also included studies that have reported epigenetic factors, such as abnormal apoptosis, enhanced oxidative stress and pro-inflammatory effects involving these nanoparticles. PMID:23170105

  1. 29 CFR 1990.131 - Priority lists for regulating potential occupational carcinogens.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... occupational carcinogens. One list should include approximately ten (10) candidates for rulemaking as Category I Potential Carcinogens; the other approximately ten (10) candidates for rulemaking as Category...

  2. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    PubMed Central

    Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M.; Armstrong, Bruce K.; Baccarelli, Andrea A.; Beland, Frederick A.; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S.; Brownson, Ross C.; Bucher, John R.; Cantor, Kenneth P.; Cardis, Elisabeth; Cherrie, John W.; Christiani, David C.; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A.; Dement, John M.; Douwes, Jeroen; Eisen, Ellen A.; Engel, Lawrence S.; Fenske, Richard A.; Fleming, Lora E.; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K.; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A.; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R.; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H.; Lynch, Charles F.; Lynge, Elsebeth; ‘t Mannetje, Andrea; McMichael, Anthony J.; McLaughlin, John R.; Marrett, Loraine; Martuzzi, Marco; Merchant, James A.; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E.; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F.; Parent, Marie-Elise; Perera, Frederica P.; Perry, Melissa J.; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B.; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M.; Rushton, Lesley; Rusiecki, Jennifer A.; Rusyn, Ivan; Samet, Jonathan M.; Sandler, Dale P.; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T.; Simonato, Lorenzo; Smith, Allan H.; Smith, Martyn T.; Spinelli, John J.; Spitz, Margaret R.; Stallones, Lorann; Stayner, Leslie T.; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W.; Stewart, Patricia A.; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E.; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G.; Ward, Elizabeth M.; Weinberg, Clarice R.; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-01-01

    Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health. Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP

  3. Cost and Schedule Analytical Techniques Development: Option 2 Year

    NASA Technical Reports Server (NTRS)

    1997-01-01

    This Final Report summarizes the activities performed by Science Applications International Corporation (SAIC) for the Option 2 Year from December 1, 1996 through November 30, 1997. The Final Report is in compliance with Paragraph 5 of Section F of the contract. This CSATD contract provides products and deliverable in the form of models, data bases, methodologies, studies and analyses for the NASA Marshall Space Flight Center's (MSFC) Engineering Cost Office (PPO3) the Program Plans and Requirements Officer (PP02), and other user organizations. Detailed Monthly Progress reports were submitted to MSFC in accordance with the contract's Statement of Work, Section TV "Reporting and Documentation". These reports spelled out each month's specific work accomplishments, deliverables submitted, major meetings held, and other pertinent information. This Final Report will summarize these activities at higher level. During this contract Option Year, SAIC expended 29,830 man-hours in tile performance of tasks called out in the Statement of Work and reported oil in this yearly Final Report. This represents approximately 16 full-time EPs. Included are the basis Huntsville-based team, plus SAIC specialists in San Diego, Ames Research Center, Chicago, and Colorado Springs performing specific tasks for which they are uniquely qualified.

  4. Effect of Chemical Mutagens and Carcinogens on Gene Expression Profiles in Human TK6 Cells

    PubMed Central

    Godderis, Lode; Thomas, Reuben; Hubbard, Alan E.; Tabish, Ali M.; Hoet, Peter; Zhang, Luoping; Smith, Martyn T.; Veulemans, Hendrik; McHale, Cliona M.

    2012-01-01

    Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes), we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose–response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti-) apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control. PMID:22723965

  5. The carcinogenic initiating and promoting properties of a lightly refined paraffinic oil.

    PubMed

    McKee, R H; Plutnick, R T; Przygoda, R T

    1989-05-01

    The dermal carcinogenic potential of some petroleum-derived liquids is related to the polycyclic aromatic hydrocarbon (PAH) content. However, repeated application of middle distillates (MDs), e.g., kerosene, diesel fuel, and heating oil, produced tumors in mouse skin. This result was unexpected since the MDs typically contain very low levels of biologically active PAHs. The present study examined the tumorigenic mechanism of a lightly refined paraffinic oil (LRPO), an MD shown to be active in mouse skin. The LRPO was separated into saturated and aromatic fractions. Whole LRPO and various fractions were tested for mutagenic activity in the Salmonella assay and for carcinogenic initiating and promoting activity. There was no evidence that any of the samples examined were mutagenic in bacteria or carcinogenic initiating agents in mouse skin. Thus no support was provided for the hypothesis that the complete tumorigenic activity of LRPO was in any way related to the presence of low levels of PAHs or to an interaction between initiating and promoting constituents. There was evidence that LRPO was a weak promoter of dimethylbenzanthracene (DMBA)-initiated mouse skin. It was also found that repeated application of LRPO produced chronic irritation and hyperplasia, and this may have been responsible for the promotional effects. Based on these data, it seemed likely that the complete carcinogenic activity of this class of products is also the result of an epigenetic process related to skin irritation. PMID:2663578

  6. Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes.

    PubMed

    Antonova, Olga; Toncheva, Draga; Grigorov, Evgeni

    2015-01-01

    Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S-transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies. PMID:26854433

  7. Rapid screening of potential human bladder carcinogens: genotoxicity in meiosis repair deficient Drosophila melanogaster.

    PubMed

    Lamm, L M; Reichert, D F; Lamm, D L

    1989-11-01

    To find a quick screen of potential bladder carcinogens, a genotoxicity test in Drosophila melanogaster stocks containing DNA repair mutations was evaluated. Meiosis repair deficient male Drosophila melanogaster mei-9, mei-41, and the double mutant mei-9-41 were allowed to mate with attached -x females on media containing the test agent. Genotoxic agents produce DNA damage which accumulates and can be lethal in mei males, whereas the attached -x females are able to repair the damage and survive. Thus, the sex ratio of the progeny is a measure of genotoxicity which can be correlated with mutagenicity and carcinogenicity. In this study, tea, coffee, and saccharin were not genotoxic (p greater than 0.3). Dose dependent toxicity was observed in bracken fern (p less than 0.001). The known mutagen and bladder carcinogen, cyclophosphamide, was highly genotoxic (p less than .001). Drosophila genotoxicity not only permits rapid screening of mutagens, but may also have advantages over other systems in the screening of potential bladder carcinogens. PMID:2509735

  8. Thirdhand Tobacco Smoke: A Tobacco-Specific Lung Carcinogen on Surfaces in Smokers’ Homes

    PubMed Central

    2014-01-01

    Introduction: Thirdhand tobacco smoke consists of substances remaining on the surfaces or in the dust of areas where people have smoked. While previous studies have demonstrated the presence of nicotine and various other constituents of tobacco smoke on surfaces in smokers’ homes, none has investigated the presence of tobacco-specific carcinogens. Methods: We used liquid chromatography-tandem mass spectrometry to analyze surface dust samples from both the homes of smokers and nonsmokers for the powerful tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Results: We positively identified NNK on surfaces in 33 of 37 smokers’ homes (700±788 pg/100cm2 [range, not detected–3,500 pg/100cm2]), but only in 3 of 19 nonsmokers’ homes (235±176 pg/100cm2 in the homes where NNK was detected [range, not detected–435 pg/100cm2]). The differences in occurrence and levels of NNK in the homes of smokers and nonsmokers were significant (p < .0001). Conclusions: The powerful tobacco-specific lung carcinogen NNK is present on surfaces in most homes occupied by smokers. Potential renters or buyers of apartments or homes should be notified if previous residents were smokers in order to avoid unnecessary exposure of their families to a potent lung carcinogen. PMID:23892827

  9. Cytochrome P-450 monooxygenase systems in aquatic species: Carcinogen metabolism and biomarkers for carcinogen and pollutant exposure

    SciTech Connect

    Stegeman, J.J. ); Lech, J.J. )

    1991-01-01

    High levels of polynuclear aromatic hydrocarbon (PAH) carcinogens commonly occur in aquatic systems where neoplasms arise in fish and other animals. Enzymes that transform PAHs can act in initiating these diseases and can indicate the contamination of fish by carcinogens and other pollutants. Cytochrome P-450 has similar roles in activating PAH carcinogens in fish and mammalian species. PAHs and many chlorinated hydrocarbons, e.g., polychlorinated biphenyls (PCBs) induce a form of cytochrome P-450 in fish that is the primary catalyst of PAH metabolism. The induction of this P-450 in fish can accelerate the disposition of hydrocarbons but can also enhance the formation of carcinogenic derivatives of PAHs. Invertebrates have lower rates of PAH metabolism than fish. The induction of P-450 forms can indicate the exposure of fish to PAHs, PCBs, and other toxic compounds. This is not restricted to carcinogens. Environmental induction has been detected in fish from contaminated areas by use of catalytic assay, antibodies to fish P-450, and cDNA probes that hybridize with P-450 messenger RNA. Application of these methods can provide sensitive biological monitoring tools that can detect environmental contamination of fish by some carcinogens and tumor promoters. The potential for using P-450 induction to detect direct-acting carcinogens and tumor promoters that are noninducers is limited, although such compounds can be expected to co-occur with pollutants that are inducers.

  10. Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

    SciTech Connect

    Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

    2014-11-01

    Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

  11. Impact of occupational carcinogens on lung cancer risk in a general population

    PubMed Central

    De Matteis, Sara; Consonni, Dario; Lubin, Jay H; Tucker, Margaret; Peters, Susan; Vermeulen, Roel CH; Kromhout, Hans; Bertazzi, Pier Alberto; Caporaso, Neil E; Pesatori, Angela C; Wacholder, Sholom; Landi, Maria Teresa

    2012-01-01