Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo.

PubMed

Weinstein, I B; Jeffrey, A M; Jennette, K W; Blobstein, S H; Harvey, R G; Harris, C; Autrup, H; Kasai, H; Nakanishi, K

1976-08-13

Evidence has been obtained that a specific isomer of a diol epoxide derivative of benzo(a)pyrene, (+/-)-7 beta,8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, is an intermediate in the binding of benzo(a)pyrene to RNA in cultured bovine bronchial mucosa. An adduct is formed between position 10 of this derivative and the 2-amino group of guanine.

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

EPA Pesticide Factsheets

In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science discussion materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

IRIS Toxicological Review of Benzo[a]pyrene (Public ...

EPA Pesticide Factsheets

EPA is developing an Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene and has released the draft assessment for public comment and external peer review. When final, the assessment will appear on the IRIS database. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

Cellular deficiency of Werner Syndrome protein or RECQ1 promotes genotoxic potential of hydroquinone and benzo[a]pyrene exposure

PubMed Central

Garige, Mamatha; Sharma, Sudha

2014-01-01

The five known RecQ helicases in humans (RECQ1, BLM, WRN, RECQL4, and RECQ5) have demonstrated roles in diverse genome maintenance mechanisms but their functions in safeguarding the genome from environmental toxicants are poorly understood. Here, we have evaluated a potential role of WRN (mutated in Werner Syndrome) and RECQ1 (the most abundant homolog of WRN) in hydroquinone and benzo[a]pyrene-induced genotoxicity. Silencing of WRN or RECQ1 expression in HeLa cells increased their sensitivity to hydroquinone and benzo[a]pyrene but elicited distinct DNA damage response. RECQ1-depleted cells exhibited increased RPA phosphorylation, Chk1 activation, and DNA double strand breaks as compared to control or WRN-depleted cells following exposure to benzo[a]pyrene treatment. Benzo[a]pyrene-induced double strand breaks in RECQ1-depleted cells were dependent on DNA-PK activity. Notably, loss of WRN in RECQ1-depleted cells ameliorated benzo[a]pyrene toxicity. Collectively, our results provide first indication of non-redundant participation of WRN and RECQ1 in protection from the potentially carcinogenic effects of benzo[a]pyrene and hydroquinone. PMID:25228686

Investigation of biological destruction of benzo[a]pyrene andpolycyclic aromatic hydrocarbons of biochar in soil

NASA Astrophysics Data System (ADS)

Okunev, R. V.; Smirnova, E. V.; Sharipova, A. R.; Gilmutdinova, I. M.; Giniyatullin, K. G.

2018-01-01

The biological decomposition of benzo[a]pyrene in the concentrations exceeding the MAC (maximum permissible concentration) level in soils by 2, 5 and 10 times was studied in laboratory conditions. The gray forest soil samples were contaminated with benzo[a]pyrene and incubated in optimum for bacterial growth soil moisture for 30 and 60 days. The residual amount of contaminant was monitored by HPLC after extraction with acetone-cyclohexane (2:1). Soil microbial activity was evaluated by measuring basal respiration (BR) and substrate-induced respiration (SID) rates of the soil by gas chromatography. The results of the experiment showed that in 60 days the amount of benzo[a]pyrene in contaminated soils decreased; however, this time was not enough for complete decomposition of pollutant. In this case, benzo[a]pyrene has a negative effect on the BR and SIR rates. Soil contamination affected the BR rate only at high doses (10 MPC), whereas the SIR was a more sensitive indicator of the toxic effect of the pollutant and significantly reacts already at concentrations at the level of 2 MPC. The combination of PAHs isolated from biochar has a strong negative effect on the values of BR and SIR.

IRIS Toxicological Review of Benzo[a]pyrene (Interagency ...

EPA Pesticide Factsheets

On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written comments on IRIS assessments submitted by other federal agencies and White House Offices are made publicly available. Accordingly, interagency comments and the interagency science consultation materials provided to other agencies, including interagency review drafts of the IRIS Toxicological Review of Benzo[a]pyrene and the charge to external peer reviewers, are posted on this site. EPA is undertaking an update of the Integrated Risk Information System (IRIS) health assessment for benzo[a]pyrene (BaP). The outcome of this project is an updated Toxicological Review and IRIS Summary for BaP that will be entered into the IRIS database.

IRIS Toxicological Review of Benzo[a]pyrene (Public Comment Draft)

EPA Science Inventory

EPA is developing an Integrated Risk Information System (IRIS) assessment of benzo[a]pyrene and has released the draft assessment for public comment and external peer review. When final, the assessment will appear on the IRIS database.

Analysis of benzo(a)pyrene in airborne particulates by gas chromatography

NASA Technical Reports Server (NTRS)

Luedecke, E.

1976-01-01

A routine method was developed to measure benzo(a)pyrene in airborne particulates. Samples were collected on a filter and the organic portion was extracted with cyclohexane. The polynuclear hydrocarbon (PNHC) fraction was separated from the aliphatics by column chromatography. An internal standard was added to the extract and a portion of it was injected into a gas chromatograph. Although the gas chromatographic method has often been reported in the literature, satisfactory separation of benzo(a)pyrene and benzo(e)pyrene has not been achieved. With the introduction of a nematic liquid crystal as the stationary phase good separation is now possible.

IRIS Toxicological Review of Benzo[a]pyrene (Interagency Science Discussion Draft)

EPA Science Inventory

In January 2017, EPA finalized the IRIS assessment of Benzo[a]pyrene. The Toxicological Review was reviewed internally by EPA and by other federal agencies and White House Offices before public release. Consistent with the May 2009 IRIS assessment development process, all written...

Mechanism-based inactivation of benzo(a)pyrene hydroxylase by aryl acetylenes and aryl olefins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, L.S.; Lu, J.Y.L.; Alworth, W.L.

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxgenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene, 3-ethynylperylene, 2-ethynylfluorene, methyl 1-pyrenyl acetylene, cis- and trans-1-(2-bromovinyl)pyrene, and 1-allylpyrene serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene hydroxylase, while 1-vinylpyrene and phenyl 1-pyrenyl acetylene do not cause a detectable suicide inhibition of benzo(a)pyrene hydroxylase. The mechanism-based loss of benzo(a)pyrene hydroxylase caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes (suicide destruction). The suicide inhibition by these aryl acetylenesmore » therefore does not involve covalent binding to the heme moiety of the monooxygenase. Nevertheless, in the presence of NADPH, /sup 3/H-labeled 1-ethynylpyrene becomes covalently attached to the cytochrome P-450 protein; the measured stoichiometry of binding is one 1-ethynylpyrene per P-450 heme unit. The authors conclude that the inhibition of benzo(a)pyrene hydroxylase produced by 1-ethynylpyrene may be related to the mechanism of suicide inhibition of P-450 activity by chloramphenicol rather than the mechanism of suicide destruction of P-450 previously described for acetylene and propyne.« less

Removal of pyrene and benzo(a)pyrene micropollutant from water via adsorption by green synthesized iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Hassan, Saad S. M.; Abdel-Shafy, Hussein I.; Mansour, Mona S. M.

2018-03-01

Polycyclic aromatic hydrocarbons (PAHs) in water are classified as organic micropollutants, which are carcinogenic even in very low concentration (ppb). In this study the green synthesized iron oxide nanoparticles (IONPs) were green synthesized at room temperature by using pomegranate peel extract. The green synthesized IONPs were used for adsorbing benzo(a)pyrene and pyrene (PAHs) from water. Factors affecting the adsorption were investigated. These factors are: nanoparticles dose, pH, temperature, and initial concentration of PAHs. The overall results showed that the maximum adsorption capacities of IONPs towards pyrene and benzo(a)pyrene were 2.8 and 0.029 mg g-1, respectively. The thermodynamic study indicated an exothermic adsorption process of pyrene and benzo(a)pyrene. The kinetic and isotherm studies were carried out. The obtained data revealed that the adsorption process follows a pseudo-second order mechanism and obeys Langmuir isotherm model. In addition, the IONPs proved to be a potential candidate for the adsorption of pyrene and benzo(a)pyrene even after five cycles of use and regeneration. The investigation was extended using semi-pilot plant to remove the studied PAHs from artificially contaminated water. The results showed that the IONPs was capable to remove the pyrene and benzo (a) pyrene at the rate of 98.5 and 99%, respectively. It also can be used as disinfectant.

USE OF MULTIPHOTON LASER SCANNING MICROSCOPY TO IMAGE BENZO[A]PYRENE AND METABOLITES IN FISH EGGS

EPA Science Inventory

Multiphoton laser scanning microscopy (MPLSM) is a promising tool to study the tissue distribution of environmental chemical contaminants during fish early life stages. One such chemical for which this is possible is benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon that a...

IRIS Toxicological Review of Benzo[a]pyrene (Interagency Science Consultation Draft)

EPA Science Inventory

On August 21, 2013, the draft Toxicological Review of Benzo[a]pyrene and the draft charge to external peer reviewers were released for public review and comment. The Toxicological Review and charge were reviewed internally by EPA and by other federal agencies and White House Offi...

Transcriptomic changes in zebrafish embryos and larvae following benzo[a]pyrene exposure

USDA-ARS?s Scientific Manuscript database

Benzo[a]pyrene (BaP) is an environmentally relevant carcinogenic and endocrine disrupting compound that causes immediate, long-term, and multigenerational health deficits in mammals and fish. Previously, we found that BaP alters DNA methylation patterns in developing zebrafish, which may affect gene...

The anti-initiator action of p-methoxyphenol phosphate upon the transformation of normal human embryo cells induced by benzo(a)pyrene.

PubMed

Găldean, D; Petraşincu, D; Stoicescu, D

1992-01-01

The association of p-methoxyphenol phosphate (10(-5)M) to benzo(a)pyrene treatment (10(-6)M) reduced significantly the anchorage independent growth and the number of transformed foci of the human embryo lung fibroblasts, after six passages from treatment application. Results from cytogenetic analysis show that p-methoxyphenol phosphate induced the decrease of numerical and structural chromosome aberration after the first passage of the treated cells. In terms of the results obtained by cytogenetic analysis the reduction of genetic instability seems to remain constant from the first to the sixth passage in the cell cultures treated with p-methoxyphenol phosphate associated to benzo(a)pyrene.

USE OF MULTIPHOTON LASER SCANNING MICROSCOPY TO IMAGE BENZO[A]PYRENE AND METABOLITES IN FISH EARLY LIFE STAGES

EPA Science Inventory

Multiphoton laser scanning micrsocopy holds promise as a tool to study the tissue distribution of environmental chemical contaminants during fish early life stage development. One such chemical for which this is possible is benzo[a]pyrene (BaP), a polyaromatic hydrocarbon that a...

Association between Mutation Spectra and Stable and Unstable DNA Adduct Profiles in Salmonella for Benzo[a]pyrene and Dibenzo[a.l]pyrene

EPA Science Inventory

Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments ha...

Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure

USDA-ARS?s Scientific Manuscript database

Benzo[a]pyrene (BaP) is an established reproductive and developmental toxicant. BaP exposure in humans and animals has been linked to infertility and multigenerational health consequences. DNA methylation is the most studied epigenetic mechanism that regulates gene expression, and mapping of methyla...

Excretion of 3-hydroxy-benzo(a)pyrene and mutagenicity in rat urine after exposure to benzo(a)pyrene.

PubMed

Jongeneelen, F J; Leijdekkers, C M; Bos, R P; Theuws, J L; Henderson, P T

1985-10-01

3-hydroxy-benzo(a)pyrene (3-OH-B(a)P) and mutagenic activity in rat urine were determined after the oral administration of benzo(a)pyrene given in three repeated doses of 10, 20 and 50 mumol kg-1. The procedure for the determination of 3-OH-B(a)P consisted of enzymic hydrolysis, separation and HPLC-analysis. The mutagenic activity of concentrated urine samples was assayed with the Salmonella typhimurium strain TA98 in the presence of S9 mix and beta-glucuronidase. The urinary excretion of 3-OH-B(a)P and mutagens showed a correlation and both increased dose-dependently during the sampling period of 6 days. Data indicated that 3-OH-B(a)P can be regarded as a reliable representative of all urinary (pre)-mutagens derived from benzo(a)pyrene and exposure of rats to benzo(a)pyrene could be detected with greater sensitivity by the HPLC assay of 3-OH-B(a)P than with the non-specific mutagenicity assay.

Evaluation of dissipation mechanisms for benzo[a]pyrene in the rhizosphere of tall fescue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Banks, M.K.; Schwab, A.P.; Lee, E.

Although polycyclic aromatic hydrocarbons are common contaminants in soil and are potentially carcinogenic and mutagenic, little is known about their fate in the soil/root environment. The impact of tall fescue (Festuca arundinacea Schreber) on chemical and biological transformations of benzo[a]pyrene in soil was investigated in a greenhouse experiment in which [sup 14]C-benzo[a]pyrene was added to soil and placed in sealed chambers with and without plants. The distribution of [sup 14]C in soil, plant tissue, and CO[sub 2] was quantified. Dissipation due to mineralization and volatilization accounted for <2% of the total [sup 14]C added in both planted and unplanted chambersmore » and was greater in the presence of plants. Plant uptake of [sup 14]C was <0.12%. Residual benzo[a]pyrene was lower in soil with plants than in the absence of plants. The majority of the [sup 14]C label was associated with the soil matrix. The presence of plants enhance the degradation of highly adsorbed, recalcitrant benzo[a]pyrene in soil.« less

Successive Mineralization and Detoxification of Benzo[a]pyrene by the White Rot Fungus Bjerkandera sp. Strain BOS55 and Indigenous Microflora

PubMed Central

Kotterman, Michiel J. J.; Vis, Eric H.; Field, Jim A.

1998-01-01

White rot fungi can oxidize high-molecular-weight polycyclic aromatic hydrocarbons (PAH) rapidly to polar metabolites, but only limited mineralization takes place. The objectives of this study were to determine if the polar metabolites can be readily mineralized by indigenous microflora from several inoculum sources, such as activated sludge, forest soils, and PAH-adapted sediment sludge, and to determine if such metabolites have decreased mutagenicity compared to the mutagenicity of the parent PAH. 14C-radiolabeled benzo[a]pyrene was subjected to oxidation by the white rot fungus Bjerkandera sp. strain BOS55. After 15 days, up to 8.5% of the [14C]benzo[a]pyrene was recovered as 14CO2 in fungal cultures, up to 73% was recovered as water-soluble metabolites, and only 4% remained soluble in dibutyl ether. Thin-layer chromatography analysis revealed that many polar fluorescent metabolites accumulated. Addition of indigenous microflora to fungal cultures with oxidized benzo[a]pyrene on day 15 resulted in an initially rapid increase in the level of 14CO2 recovery to a maximal value of 34% by the end of the experiments (>150 days), and the level of water-soluble label decreased to 16% of the initial level. In fungal cultures not inoculated with microflora, the level of 14CO2 recovery increased to 13.5%, while the level of recovery of water-soluble metabolites remained as high as 61%. No large differences in 14CO2 production were observed with several inocula, showing that some polar metabolites of fungal benzo[a]pyrene oxidation were readily degraded by indigenous microorganisms, while other metabolites were not. Of the inocula tested, only PAH-adapted sediment sludge was capable of directly mineralizing intact benzo[a]pyrene, albeit at a lower rate and to a lesser extent than the mineralization observed after combined treatment with white rot fungi and indigenous microflora. Fungal oxidation of benzo[a]pyrene resulted in rapid and almost complete elimination of its high mutagenic potential, as observed in the Salmonella typhimurium revertant test performed with strains TA100 and TA98. Moreover, no direct mutagenic metabolite could be detected during fungal oxidation. The remaining weak mutagenic activity of fungal cultures containing benzo[a]pyrene metabolites towards strain TA98 was further decreased by subsequent incubations with indigenous microflora. PMID:9687440

REACTIONS OF BENZO[A]PYRENE-7,8-QUINONE WITH DEOXYGUANOSINE AND DEOXYADENOSINE AT PHYSIOLOGICAL pH: IDENTIFICATION AND CHARACTERIZATION OF STABLE ADDUCTS

EPA Science Inventory

Reactions of Benzo[a]pyrene-7,8-quinone with Deoxyguanosine and Deoxyadenosine at Physiological pH: Identification and Characterization of Stable Adducts

Narayanan Balu, William T. Padgett, Guy Lambert, Adam E. Swank,
Ann M. Richard, and Stephen Nesnow

Environmen...

ON BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED IN LUNG TISSUE OF MICE

EPA Science Inventory

On Benzo [a] pyrene Derived DNA Adducts Formed in Lung Tissue of Mice
The previously identified major DNA adducts of benzo[a]pyrene (BP) in vitro and in vivo are the stable and unstable adducts formed by reaction of the bay-region diol epoxide of BP (BPDE) and BP radical catio...

ADDITIVITY OF IN VIVO MUTATION INDUCTION BY CUMULATIVE EXPOSURES TO BENZO[A]PYRENE OR DIBENZO[A,L]PYRENE

EPA Science Inventory

Dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P) are polycyclic aromatic hydrocarbons (PAH) found in cigarette smoke condensate, coal combustion processes and in some environmental pollutants. In this study, we investigated the effect of dosing regimen on the mutagenicity...

IDENTIFICATION AND QUANTITATION OF BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED AT LOW ADDUCTION LEVEL IN MICE LUNG TISSUE

EPA Science Inventory

The two major metabolic pathways of benzo[a]pyrene (BP), as well as other polycyclic aromatic hydrocarbons, that allow for the induction of DNA lesions are monooxygenation that results in diol epoxides (BPDE), and one-electron oxidation that yields a BP radical cation. The DNA ad...

FORMATION AND PERSISTANCE OF DNA ADDUCTS IN THE LIVER OF BROWN BULLHEADS EXPOSED TO BENZO(A)PYRENE

EPA Science Inventory

The formation and persistence of benzo[a]pyrene (BP)-DNA adducts in the liver of brown bullheads (Ictalurus nebulosus) treated with the hydrocarbon (20 mg/kg body wt, i.p.) was investigated using the 32P-postlabeling assay. he highest level of covalent binding of BP to liver DNA ...

Temporal aspects of tumorigenic response to individual and mixed carcinogens. [Response of mouse skin to benzo(a)pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert, R.E.; Burns, F.J.

1976-02-01

Results are reported from experiments that involved either single or multiple doses of benzo(a)pyrene in mouse skin followed by prolonged observation. Preliminary results indicate linearity in dose and time and no evidence of recovery or enhancement for multiple doses of initiator given for extended periods of time. (auth)

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.

INTERSPECIES COMPARISONS OF BENZO(A)PYRENE METABOLISM AND DNA-ADDUCT FORMATION IN CULTURED HUMAN AND ANIMAL BLADDER AND TRACHEOBRONCHIAL TISSUES

EPA Science Inventory

Cultured bladder and tracheobronchial explants from human, monkey, dog, hamster, and rat were used to study the metabolism, covalent binding to DNA, and DNA:adduct formation of (3H0benzo(a)pyrene (BP). Both organs from all species formed large amounts (40 to 70% of total 3H in th...

Benzo[a]pyrene co-metabolism in the presence of plant root extracts and exudates: Implications for phytoremediation.

PubMed

Rentz, Jeremy A; Alvarez, Pedro J J; Schnoor, Jerald L

2005-08-01

Benzo[a]pyrene, a high molecular weight (HMW) polycyclic aromatic hydrocarbon (PAH) was removed from solution by Sphingomonas yanoikuyae JAR02 while growing on root products as a primary carbon and energy source. Plant root extracts of osage orange (Maclura pomifera), hybrid willow (Salix albaxmatsudana), or kou (Cordia subcordata), or plant root exudates of white mulberry (Morus alba) supported 15-20% benzo[a]pyrene removal over 24 h that was similar to a succinate grown culture and an unfed acetonitrile control. No differences were observed between the different root products tested. Mineralization of (14)C-7-benzo[a]pyrene by S. yanoikuyae JAR02 yielded 0.2 to 0.3% (14)CO(2) when grown with plant root products. Collectively, these observations were consistent with field observations of enhanced phytoremediation of HMW PAH and corroborated the hypothesis that co-metabolism may be a plant/microbe interaction important to rhizoremediation. However, degradation and mineralization was much less for root product-exposed cultures than salicylate-induced cultures, and suggested the rhizosphere may not be an optimal environment for HMW PAH degradation by Sphingomonas yanoikuyae JAR02.

Validity of empirical models of exposure in asphalt paving

PubMed Central

Burstyn, I; Boffetta, P; Burr, G; Cenni, A; Knecht, U; Sciarra, G; Kromhout, H

2002-01-01

Aims: To investigate the validity of empirical models of exposure to bitumen fume and benzo(a)pyrene, developed for a historical cohort study of asphalt paving in Western Europe. Methods: Validity was evaluated using data from the USA, Italy, and Germany not used to develop the original models. Correlation between observed and predicted exposures was examined. Bias and precision were estimated. Results: Models were imprecise. Furthermore, predicted bitumen fume exposures tended to be lower (-70%) than concentrations found during paving in the USA. This apparent bias might be attributed to differences between Western European and USA paving practices. Evaluation of the validity of the benzo(a)pyrene exposure model revealed a similar to expected effect of re-paving and a larger than expected effect of tar use. Overall, benzo(a)pyrene models underestimated exposures by 51%. Conclusions: Possible bias as a result of underestimation of the impact of coal tar on benzo(a)pyrene exposure levels must be explored in sensitivity analysis of the exposure–response relation. Validation of the models, albeit limited, increased our confidence in their applicability to exposure assessment in the historical cohort study of cancer risk among asphalt workers. PMID:12205236

IDENTIFICATION AND CHARACTERIZATION OF NOVEL STABLE DEOXYGUANNOSINE AND DEOXYADENOSINE ADDUCTS OF BENZO[A]PYRENE-7,8-QUINONE FROM REACTIONS AT PHYSIOLOGICAL PH

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is an archetypal member of the family of polycyclic aromatic hydrocarbons (PAHs) and is a widely-distributed environmental pollutant. B[a]P is known to induce cancer in animals and B[a]P-containing complex mixtures are human carcinogens. B[a]P exerts its ge...

Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-B[a]P-7,8-diol-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from r...

Monitoring of polycyclic aromatic hydrocarbons (PAH) in food supplements containing botanicals and other ingredients on the Dutch market.

PubMed

Martena, M J; Grutters, M M P; De Groot, H N; Konings, E J M; Rietjens, I M C M

2011-01-01

Food supplements can contain polycyclic aromatic hydrocarbons (PAH). The European Food Safety Authority (EFSA) has defined 16 priority PAH that are both genotoxic and carcinogenic and identified eight priority PAH (PAH8) or four of these (PAH4) as good indicators of the toxicity and occurrence of PAH in food. The current study aimed to determine benzo[a]pyrene and other EFSA priority PAH in different categories of food supplements containing botanicals and other ingredients. From 2003 to 2008, benzo[a]pyrene exceeded the limit of quantification (LOQ) in 553 (44%) of 1258 supplements with a lower-bound mean of 3.37 µg kg(-1). In 2008 and 2009, benzo[a]pyrene and 12 other EFSA priority PAH were determined in 333 food supplements. Benzo[a]pyrene exceeded the LOQ in 210 (63%) food supplements with a lower-bound mean of 5.26 µg kg(-1). Lower-bound mean levels for PAH4 and PAH8(-indeno[1,2,3-cd]pyrene) were 33.5 and 40.5 µg kg(-1), respectively. Supplements containing resveratrol, Ginkgo biloba, St. John's wort and propolis showed relatively high PAH4 levels in 2008 and 2009. Before 2008, supplements with these ingredients and also dong quai, green tea or valerian contained relatively high benzo[a]pyrene levels. On average, PAH4 intake resulting from food supplement use will be at the lower end of the range of contributions of main food groups to PAH4 exposure, although individual food supplements can contribute significantly to PAH4 exposure. Regular control of EFSA indicator PAH levels in food supplements may prove a way forward to reduce further the intake of PAH from food.

Photodegradation of polycyclic aromatic hydrocarbons in soils under a climate change base scenario.

PubMed

Marquès, Montse; Mari, Montse; Audí-Miró, Carme; Sierra, Jordi; Soler, Albert; Nadal, Martí; Domingo, José L

2016-04-01

The photodegradation of polycyclic aromatic hydrocarbons (PAHs) in two typical Mediterranean soils, either coarse- or fine-textured, was here investigated. Soil samples, spiked with the 16 US EPA priority PAHs, were incubated in a climate chamber at stable conditions of temperature (20 °C) and light (9.6 W m(-2)) for 28 days, simulating a climate change base scenario. PAH concentrations in soils were analyzed throughout the experiment, and correlated with data obtained by means of Microtox(®) ecotoxicity test. Photodegradation was found to be dependent on exposure time, molecular weight of each hydrocarbon, and soil texture. Fine-textured soil was able to enhance sorption, being PAHs more photodegraded than in coarse-textured soil. According to the EC50 values reported by Microtox(®), a higher detoxification was observed in fine-textured soil, being correlated with the outcomes of the analytical study. Significant photodegradation rates were detected for a number of PAHs, namely phenanthrene, anthracene, benzo(a)pyrene, and indeno(123-cd)pyrene. Benzo(a)pyrene, commonly used as an indicator for PAH pollution, was completely removed after 7 days of light exposure. In addition to the PAH chemical analysis and the ecotoxicity tests, a hydrogen isotope analysis of benzo(a)pyrene was also carried out. The degradation of this specific compound was associated to a high enrichment in (2)H, obtaining a maximum δ(2)H isotopic shift of +232‰. This strong isotopic effect observed in benzo(a)pyrene suggests that compound-specific isotope analysis (CSIA) may be a powerful tool to monitor in situ degradation of PAHs. Moreover, hydrogen isotopes of benzo(a)pyrene evidenced a degradation process of unknown origin occurring in the darkness. Copyright © 2016 Elsevier Ltd. All rights reserved.

ASSOCIATION BETWEEN MUTATION SPECTRUM AND PERSISTENT DNA ADDUCT PROFILE IN SALMONELLA FOR BENZO[A]PYRENE AND DIBENZO[A]PYRENE

EPA Science Inventory

Dibenzo[a,l]pyrene (DB[a1]P) is less prevalent in the environment but 100-200X more carcinogenic in rodents than benzo[a]pyrene (B[a]P) .B[a]P induces most of its adducts on G, whereas DB[a,1]P produces most its adducts on A. Using the Salmonella mutagenicity assay, we have exami...

Hygienic characteristics of carbon black used in tyre production.

PubMed

Rogaczewska, T; Ligocka, D; Nowicka, K

1989-01-01

Seven types of carbon black used in type production were subjected to hygienic evaluation. The coal tar pitch volatiles (CTPVs), toluene solubles, were determined by the gravimetric method and benzo/a/pyrene by HPLC with a spectrophotometric detector. Toluene solubles were found to amount to 0.12-0.25% (by weight). Benzo/a/pyrene (1.44-3.07 ppm) was detected in five out of the seven carbon blacks examined.

COMPARISON OF BLOOD PROTEIN AND TARGET ORGAN DNA AND PROTEIN BINDING FOLLOWING TOPICAL APPLICATION OF BENZO[A]PYRENE AND 7H-DIBENZO[C,G]CARBAZOLE TO MICE

EPA Science Inventory

7H-Dibenzo[c,g]carbazole (DBC) induces skin and liver tumors in mice following topical application, whereas benzo[a]pyrene (BP) induces only skin tumors. DBC also binds to liver DNA to a much greater extent than does BP. The present study examined factors that might account for t...

PENTACHLOROPHENOL POTENTIATES BENZO[A]PYRENE DNA ADDUCT FORMATION IN ADULT BUT NOT INFANT B6C3F1 MALE MICE

EPA Science Inventory

Abstract

The objective of this study is to determine whether pentachlorophenol (PCP) alters benzo[a]pyrene (B[a]P) induced DNA adduct formation in infant and adult B6C3Fl mice. Mice were exposed to 55 ug B[a]P/g body weight (BW) alone and in combination with several dose...

Mutations Induced by Benzo[a]pyrene and Dibenzo[a,l]pyrene in lacI Transgenic B6C3F1 Mouse Lung Result from Stable DNA Adducts

EPA Science Inventory

Dibenzo[a,l]pyrene (DB[a,l]P) and benzo[a]pyrene (B[a]P) are carcinogenic polycyclic aromatic hydrocarbons (PAH) that are each capable of forming a variety of covalent adducts with DNA. Some of the DNA adducts formed by these PAHs have been demonstrated to spontaneously depurina...

K-Ras mutant fraction in A/J mouse lung increases as a function of benzo[a]pyrene dose

EPA Science Inventory

K-Ras mutant fraction (MF) was measured to examine the default assumption of low dose linearity in the benzo[a]pyrene (B[a]P) mutational response. Groups of ten male A/J mice (7-9 weeks-old) received a single i.p. injection of 0, 0.05, 0.5, 5, or 50 mg/kg B[a]P, and were sacrifi...

Enhanced oxidation of benzo[a]pyrene by crude enzyme extracts produced during interspecific fungal interaction of Trametes versicolor and Phanerochaete chrysosporium.

PubMed

Qian, Linbo; Chen, Baoliang

2012-01-01

The effects of interspecific fungal interactions between Trametes versicolor and Phanerochaete chrysosporium on laccase activity and enzymatic oxidation of polycyclic aromatic hydrocarbons (PAHs) were investigated. A deadlock between the two mycelia rather than replacement of one fungus by another was observed on an agar medium. The laccase activity in crude enzyme extracts from interaction zones reached a maximum after a 5-day incubation, which was significantly higher than that from regions of T. versicolor or P. chrysosporium alone. The enhanced induction of laccase activity lasted longer in half nutrition than in normal nutrition. A higher potential to oxidize benzo[a]pyrene by a crude enzyme preparation extracted from the interaction zones was demonstrated. After a 48 hr incubation period, the oxidation of benzo[a]pyrene by crude enzyme extracts from interaction zones reached 26.2%, while only 9.5% of benzo[a]pyrene was oxidized by crude extracts from T. versicolor. The oxidation was promoted by the co-oxidant 2,2'-azinobis-3-ethylbenzthiazoline-6-sulphonate diammonium salt (ABTS). These findings indicate that the application of co-culturing of white-rot fungi in bioremediation is a potential ameliorating technique for the restoration of PAH-contaminated soil.

THE EFFECT OF PENTACHLOROPHENOL ON DNA ADDUCT FORMATION IN C57B1/6 TRP53 +/+ AND C57B16 TRP53 -/- MICE EXPOSED TO BENZO[A]PYRENE MAY BE ASSOCIATED WITH P53 FUNCTION.

EPA Science Inventory

Abstract

Previous studies have shown that pentachlorophenol (PCP) has both potentiative and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has been suggested that these effects are due to inhibition and/or induction of enzymes involved in the biotr...

BENZO[A]PYRENE-7,8-QUINONE FORMS COVALENT-DNA ADDUCTS IN VITRO BUT NONE WERE DETECTED IN THE LUNGS OR LIVERS OF STRAIN A/J MICE IN VIVO

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of B[a]P-7,8-dio1-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: 1.] The induction of apurinic sites from radical cati...

Hasse diagram as a green analytical metrics tool: ranking of methods for benzo[a]pyrene determination in sediments.

PubMed

Bigus, Paulina; Tsakovski, Stefan; Simeonov, Vasil; Namieśnik, Jacek; Tobiszewski, Marek

2016-05-01

This study presents an application of the Hasse diagram technique (HDT) as the assessment tool to select the most appropriate analytical procedures according to their greenness or the best analytical performance. The dataset consists of analytical procedures for benzo[a]pyrene determination in sediment samples, which were described by 11 variables concerning their greenness and analytical performance. Two analyses with the HDT were performed-the first one with metrological variables and the second one with "green" variables as input data. Both HDT analyses ranked different analytical procedures as the most valuable, suggesting that green analytical chemistry is not in accordance with metrology when benzo[a]pyrene in sediment samples is determined. The HDT can be used as a good decision support tool to choose the proper analytical procedure concerning green analytical chemistry principles and analytical performance merits.

BENZO[A]PYRENE AND ITS K-REGION DIOL INDUCE DNA DAMAGE IN C3H10T1/2C18 CELLS AS MEASURED BY THE ALKALINE SINGLE CELL GEL (COMET) ASSAY

EPA Science Inventory

160. Benzo[a]pyrene and its K-region diol induce DNA damage in C3HlOTl/2Cl8 cells as measured by the alkaline single cell gel (Comet) assay

In a continuing series of studies on the genotoxicity ofK-region dihydrodiols of polycyclic aromatic hydrocarbons, we have repo...

Particulate polycyclic aromatic hydrocarbons (PAH) in the atmosphere of Bizerte city, Tunisia.

PubMed

Ben Hassine, S; Hammami, B; Ben Ameur, W; El Megdiche, Y; Barhoumi, B; Driss, M R

2014-09-01

The particle-phase concentrations of polycyclic aromatic hydrocarbons (PAH) were determined in 13 air samples collected in an urban area of Bizerte (Tunisia) during 2009-2010. Atmospheric particulate samples were extracted by ultrasonic bath and analyzed by high-performance liquid chromatography with fluorescence detection. PAH were found in all the analyzed air samples and the most abundant compounds were pyrene, fluoranthene, benzo[g,h,i]perylene, benzo[b]fluoranthene, chrysene and benzo[a]pyrene. ∑14-PAH concentrations ranging from 9.38 to 44.81 ng m(-3) with mean value of 25.39 ng m(-3). PAH diagnostic ratio source analysis revealed gasoline and diesel vehicular emissions as major sources. The mean total benzo[a]pyrene toxicity equivalent calculated for samples was 3.66 ng m(-3) and the mean contribution of the carcinogenic potency of benzo[a]pyrene was determined to be 55.8 %. Concentrations of particulate PAH in Bizerte city atmosphere were approximately eight times greater than sampled at a nearby rural site.

Determination of benzo[a]pyrene in cigarette mainstream smoke by using mid-infrared spectroscopy associated with a novel chemometric algorithm.

PubMed

Zhang, Yan; Zou, Hong-Yan; Shi, Pei; Yang, Qin; Tang, Li-Juan; Jiang, Jian-Hui; Wu, Hai-Long; Yu, Ru-Qin

2016-01-01

Determination of benzo[a]pyrene (BaP) in cigarette smoke can be very important for the tobacco quality control and the assessment of its harm to human health. In this study, mid-infrared spectroscopy (MIR) coupled to chemometric algorithm (DPSO-WPT-PLS), which was based on the wavelet packet transform (WPT), discrete particle swarm optimization algorithm (DPSO) and partial least squares regression (PLS), was used to quantify harmful ingredient benzo[a]pyrene in the cigarette mainstream smoke with promising result. Furthermore, the proposed method provided better performance compared to several other chemometric models, i.e., PLS, radial basis function-based PLS (RBF-PLS), PLS with stepwise regression variable selection (Stepwise-PLS) as well as WPT-PLS with informative wavelet coefficients selected by correlation coefficient test (rtest-WPT-PLS). It can be expected that the proposed strategy could become a new effective, rapid quantitative analysis technique in analyzing the harmful ingredient BaP in cigarette mainstream smoke. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of white, red and black ginseng on physicochemical properties and ginsenosides.

PubMed

Jin, Yan; Kim, Yeon-Ju; Jeon, Ji-Na; Wang, Chao; Min, Jin-Woo; Noh, Hae-Yong; Yang, Deok-Chun

2015-06-01

A systematic comparison of the ginsenosides and physicochemical properties of white ginseng (WG), red ginseng (RG) and black ginseng (BG) was performed. The purpose of the present study was to identify the effects of the physicochemical properties by steaming process. During the steaming process, ginsenosides transform into specific ginsenosides by hydrolysis, dehydration and isomerization at C-3, C-6 or C-20. Steaming ginseng led to a significant increase in reducing sugar, acidic polysaccharide and phenolic compounds content. Antioxidative properties were investigated using the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity, compared with BHA (Butylated hydroxyanisole). RG and BG exhibited higher antioxidant activity than WG. The maximum residue level for Benzo(a)pyrene was established to 5 μg/kg in food products. The levels of benzo(a)pyrene in WG and RG were not detected. Benzo(a)pyrene was detected in the BG, the content was 0.17 μg/kg. The scientific achievements of the present study could help consumers to choose different type of ginseng products available on the market.

Polycyclic aromatic hydrocarbons in Italian preserved food products in oil.

PubMed

Sannino, Anna

2016-06-01

A method based on gas chromatography/ tandem mass spectrometry was used to assess levels of 16 EU priority polycyclic aromatic hydrocarbons (PAHs) in 48 preserved food products in oil including foods such as vegetables in oil, fish in oil and oil-based sauces obtained from the Italian market. The benzo[a]pyrene concentrations ranged from <0.04 to 0.40 µg kg(-1), and 72.9% of the samples showed detectable levels of this compound. The highest contamination level was observed for chrysene with three additional PAHs (benzo[a]anthracene, benzo[b]fluoranthene and benzo[c]fluorene) giving mean values higher than the mean value for benzo[a]pyrene. Chrysene was detected in all the samples at concentrations ranging from 0.07 to 1.80 µg kg(-1) (median 0.31 µg kg(-1)). The contamination expressed as PAH4 (sum of benzo(a)pyrene, chrysene, benzo(a)anthracene and benzo(b)fluoranthene), for which the maximum tolerable limit has been set by Commission Regulation (EU) No. 835/2011, varied between 0.10 and 2.94 µg kg(-1).

Evaluation of biomarkers in plasma, blood, and urine samples from coke oven workers: significance of exposure to polycyclic aromatic hydrocarbons.

PubMed Central

Ovrebø, S; Haugen, A; Farmer, P B; Anderson, D

1995-01-01

OBJECTIVE--The aim was to assess the significance of two biomarkers; antibody to benzo(a)pyrene DNA adducts and concentration of hydroxyethylvaline haemoglobin adducts in samples from a well studied group of coke oven workers. As a measure of exposure we have used 1-hydroxypyrene in urine. METHODS--Urine and blood samples were collected from coke oven workers and a control group. Samples from coke oven plant workers were collected in January and June. 1-Hydroxypyrene was measured in urine by high performance liquid chromatography (HPLC), antibodies to benzo(a)pyrene DNA adducts were measured by ELISA and hydroxyethylvaline haemoglobin adducts were measured by gas chromatography-mass spectrometry (GC-MS). RESULTS--Mean urinary 1-hydroxypyrene in samples from coke oven workers varied from 1.11 to 5.53 umol/mol creatinine and 0.14 umol/mol creatinine in the control group. Workers at the top side had the highest values of urinary 1-hydroxypyrene. Antibody to benzo(a)pyrene DNA adducts did not correlate with either 1-hydroxypyrene nor length of work at the coke oven plant. But antibody concentration in samples collected in January was predictive of the concentration in samples collected in June. A small non-significant increase in hydroxyethylvaline haemoglobin adducts was found in samples from coke oven workers relative to the control group when comparing smokers and nonsmokers separately. CONCLUSION--1-Hydroxypyrene correlates well with exposure groups based on job description. Antibodies to benzo(a)-pyrene DNA adducts was related to people and not exposure. Work at a coke oven plant might lead to increased hydroxyethylvaline haemoglobin adducts. PMID:8535495

Effects of benzo[a]pyrene dietary intake to antioxidative enzymes of Lymantria dispar (Lepidoptera: Lymantriidae) larvae from unpolluted and polluted forests.

PubMed

Gavrilović, Anja; Ilijin, Larisa; Mrdaković, Marija; Vlahović, Milena; Mrkonja, Aleksandra; Matić, Dragana; Perić-Mataruga, Vesna

2017-07-01

Anthropogenic activity in industrial development has imposed great threats to the environment and wildlife in the form of persistent organic pollutants. Polycyclic aromatic hydrocarbons (PAH) tend to accumulate in vegetation foliage which is the main food source of polyphagous insect species Lymantria dispar L. Origin and multigenerational adaptation of L. dispar population to environmental challenges strongly condition the enzymes' sensitivity to pollutants. In this study, our aim was to investigate response of the superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST) to the chronic dietary exposure of benzo[a]pyrene in the midgut tissues and hemolymph of two L. dispar populations originating from unpolluted and polluted forest habitat. Midgut tissue of the larvae from the polluted forest showed significant increase in SOD, CAT and GST activity, while in unpolluted forest's larvae SOD and CAT showed elevated activities in hemolymph. L. dispar populations adapted to different level of pollution in their environment and expressed distinct tissue-dependent antioxidative enzyme sensitivity to benzo[a]pyrene diet, implying high potential for further elucidation of these enzymes as molecular biomarkers. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel method for the rapid detection of benzo(a)pyrene in liquid milk by dimethyl sulfoxide selectively enhanced synchronous fluorescence spectrometry.

PubMed

Lin, Li-Rong; Luo, He-Dong; Li, Xiu-Ying; Li, Na; Zhou, Na; Jia, Yu-Zhu; Liu, Yi-Hong; Li, Yao-Qun

2014-01-01

Based on the high solubility efficiency and strong fluorescence response of benzo(a)pyrene (BaP) in dimethyl sulfoxide in combination with the high-performance derivative constant-energy synchronous fluorescence spectroscopic (DCESFS) technique, a simple, sensitive and economic method was developed for the determination of BaP in liquid milk. This method comprises ultrasound-assisted solvent extraction, solvent replacement and DCESFS detection. No saponification or other tedious clean-up procedures were needed. The recoveries of BaP in different milk samples were greater than 82%. Detection limits in full- and low-fat milk were 0.03 and 0.04 μg kg(-1), respectively.

Occupational exposure to coal tar pitch volatiles, benzo/a/pyrene and dust in tyre production.

PubMed

Rogaczewska, T; Ligocka, D

1994-01-01

Occupational exposure to coal tar pitch volatiles (CTPVs), benzo/a/pyrene (BaP) and dust was evaluated by means of individual measurements carried out in 80 workers and by stationary measurements on 16 work-posts in two divisions of the tyre producing plant. Dust and coal tar pitch volatiles concentrations in the air were determinated by the gravimetric method, measured, in the case of CPTVs, benzene-soluble fraction (BSF) with ultrasonic extraction. Benzo/a/pyrene analysis was performed using high performance liquid chromato-graphy (HPLC) with a spectrofluorimetric detector. It was found that nearly all personal sampling results for BaP were within the range < 4 divided by 142 ng/m3, except for the exposure of workers employed at weighing the raw materials (3,470-6,060 ng/m3) in the Semiproducts Division. Attention should be paid to the recorded CTPVs concentrations (benzene solubles). About 56% of the Vulcanizing Division workers and about 90% of the Semiproducts Division workers were exposed to these substances at concentrations of over 0.2 mg/m3 (hygienic standard for benzene solubles in USA). Exposure to dust (of high respirable fraction percentage > 90%) which exceeded the admissible value (4 mg/m3) was found mainly only in the workers of the Semiproducts Division at some work-posts.

Ambient air levels and health risk assessment of benzo(a)pyrene in atmospheric particulate matter samples from low-polluted areas: application of an optimized microwave extraction and HPLC-FL methodology.

PubMed

de la Gala Morales, María; Holgado, Fernando Rueda; Marín, Ma Rosario Palomo; Blázquez, Lorenzo Calvo; Gil, Eduardo Pinilla

2015-04-01

A new methodology involving a simple and fast pretreatment of the samples by microwave-assisted extraction and concentration by N2 stream, followed by HPLC with fluorescence detection, was used for determining the concentration of benzo(a)pyrene (BaP) in atmospheric particulate matter (PM10 fraction). Obtained LOD, 1.0 × 10(-3) ng/m(3), was adequate for the analysis of benzo(a)pyrene in the samples, and BaP recovery from PAH in Fine Dust (PM10-like) certified reference material was nearly quantitative (86%). The validated procedure was applied for analyzing 115 PM10 samples collected at different sampling locations in the low-polluted area of Extremadura (Southwest Spain) during a monitoring campaign carried out in 2011-2012. BaP spatial variations and seasonal variability were investigated as well as the influence of meteorological conditions and different air pollutants concentrations. A normalized protocol for health risk assessment was applied to estimate lifetime cancer risk due to BaP inhalation in the sampling areas, finding that around eight inhabitants per million people may develop lung cancer due to the exposition to BaP in atmospheric particulates emitted by the investigated sources.

Effect of chimneys on indoor air concentrations of PM 10 and benzo[a]pyrene in Xuan Wei, China

NASA Astrophysics Data System (ADS)

Tian, Linwei; Lan, Qing; Yang, Dong; He, Xingzhou; Yu, Ignatius T. S.; Hammond, S. Katharine

This paper reports the effect of chimneys in reducing indoor air pollution in a lung cancer epidemic area of rural China. Household indoor air pollution concentrations were measured during unvented burning (chimneys blocked) and vented burning (chimneys open) of bituminous coal in Xuan Wei, China. Concentrations of particulate matter with an aerodynamic diameter of 10 μm or less (PM 10) and of benzo[a]pyrene (BaP) were measured in 43 homes during normal activities. The use of chimneys led to significant decreases in indoor air concentrations of particulate matter with an aerodynamic diameter of 10 μm or less (PM 10) by 66% and of benzo[a]pyrene (BaP) by 84%. The average BaP content of PM 10 also decreased by 55% with the installation of a chimney. The reduction of indoor pollution levels by the installation of a chimney supports the epidemiology findings on the health benefits of stove improvement. However, even in the presence of a chimney, the indoor air concentrations for both PM 10 and BaP still exceeded the indoor air quality standards of China. Movement up the energy ladder to cleaner liquid or gaseous fuels is probably the only sustainable indoor air pollution control measure.

Detecting points as developmental delay based on the life-history development and urosome deformity of the harpacticoid copepod, Tigriopus japonicus sensu lato, following exposure to benzo(a)pyrene.

PubMed

Bang, Hyun Woo; Lee, Wonchoel; Kwak, Inn-Sil

2009-09-01

To identify ecotoxicological responses to an endocrine disrupter, benzo(a)pyrene, we examined the life-history of the harpacticoid copepod, Tigriopus japonicus sensu lato. Based on the life-history of copepods, survival rate of nauplii (NSR) and copepodites (CSR), copepodite emergence day (CED) and adult male emergence day (AMED), sex ratio (MER), brooding success rate (BSR), and first brooding day of adult females (FBD) were measured. Significant differences were observed in the survival and development of nauplii (NSR and CED) and sex ratio (MER) of exposed and non-exposed copepods. Moreover, high concentration of BaP can be lethal to copepodite and exhibited a delay of growth. In this study, the CED and AMED among ecotoxicological response based on life-history developments were delayed and the body characteristics decreased in response to exposure to benzo(a)pyrene. The dwarfism and urosome deformity of the T. japonicus s.l. was exhibited in response to chemical exposure. Specifically, the body characteristics and biomass of dwarf copepods that had been exposed to benzo(a)pyrene were 30% and 50% lower than the control group, respectively. The incidence of abnormal urosomes was divided into two types. The first deformity type was signs of shrinkage in the middle of the urosome or the entire urosome was narrower than those of the control organisms. In the second type, the anal somite and the distal side of the urosome had abnormally swelled. Taken together, the nauplii and copepodid development of T. japonicus s.l. can be used as a useful biomaker for detecting developmental delay based on their entire life-history. In addition, the urosome deformity was used a good potential monitoring tool invading various chemicals and environmental contamination into water system.

/sup 32/P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl, and benzo(a)pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, L.J.; Disher, R.M.; Reddy, M.V.

1986-06-01

Transplacental exposure of fetuses to carcinogens is known to induce tumors in the offspring, often with a high incidence and short latency. While covalent adduction of DNA appears to be essential for tumor initiation, little is known about the binding of carcinogens to the DNA of fetal tissues. A sensitive /sup 32/P-postlabeling method enabled us to study the binding of the environmental carcinogens safrole (600 mumol/kg p.o.), 4-aminobiphenyl (800 mumol/kg), and benzo(a)pyrene (200 mumol/kg) to the DNA of various maternal and fetal tissues after administration of test carcinogens to pregnant ICR mice on day 18 of gestation. The results showmore » that these carcinogens bound to the DNA of maternal and fetal liver, lung, kidney, heart, brain, intestine, skin, maternal uterus, and placenta, with organ-specific quantitative and qualitative differences. It was possible for the first time to analyze DNA adduct patterns in minute amounts of tissue, for example those available from fetal heart. The covalent binding index 24 h after safrole treatment was estimated for the different organs and ranged from 0.1 to 247 and 0.1 to 5.8 for maternal and fetal DNA, respectively. Covalent binding index values of 0.2 to 13 and 0.1 to 0.3 for maternal and fetal DNA, respectively, were found for 4-aminobiphenyl. Benzo(a)pyrene treatment yielded covalent binding index values of 0.6 to 6.5 and 0.3 to 0.7 for maternal and fetal DNA, respectively. In both maternal and fetal tissues, safrole exhibited preferential binding to liver DNA. 4-Aminobiphenyl bound preferentially to DNA of maternal liver and kidney but showed no preference among fetal tissues. Benzo(a)pyrene exhibited weak tissue preference in both maternal and fetal organs.« less

EGF-Receptor Phosphorylation and Downstream Signaling are Activated by Benzo[a]pyrene 3,6-quinone and Benzo[a]pyrene 1,6-quinone in Human Mammary Epithelial Cells

PubMed Central

Rodríguez-Fragoso, Lourdes; Melendez, Karla; Hudson, Laurie; Lauer, Fredine T.; Burchiel, Scott W.

2013-01-01

Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly mutagenic and carcinogenic metabolites. Previous studies in this laboratory have shown that benzo(a)pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to induce epidermal growth factor receptor (EGFR) cell signaling through the production of reactive oxygen species. Recently, we have reported that BPQs have the potential to induce the expression of genes involved in numerous pathways associated with cell proliferation and survival in human mammary epithelial cells. In the present study we demonstrated that BPQs not only induced EGFR tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine phosphorylation of phospholipase C-γ1 and several signal transducers and activators of transcription (STATs). The effects of BPQs were evaluated in a model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 μM), induced EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC-γ1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a proposed docking site for PLC-γ1 on the EGFR. Additionally, we found that BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures. Although the pattern of phosphorylation at EGFR, PLC-γ1 and STATs were quite similar to those induced by EGF, an important difference between BPQ-mediated signaling of the EGFR was observed. Signaling produced by EGF ligand produced a rapid disappearance of EGFR from the cell surface, whereas BPQ signaling maintained EGFR receptors on the cell membrane. Thus, the results of these studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by EGFR expression, and a prolonged transactivation of EGFR leading to downstream cell signaling pathways. PMID:19166869

EGF-receptor phosphorylation and downstream signaling are activated by benzo[a]pyrene 3,6-quinone and benzo[a]pyrene 1,6-quinone in human mammary epithelial cells.

PubMed

Rodríguez-Fragoso, Lourdes; Melendez, Karla; Hudson, Laurie G; Lauer, Fredine T; Burchiel, Scott W

2009-03-15

Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly mutagenic and carcinogenic metabolites. Previous studies in this laboratory have shown that benzo[a]pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to induce epidermal growth factor receptor (EGFR) cell signaling through the production of reactive oxygen species. Recently, we have reported that BPQs have the potential to induce the expression of genes involved in numerous pathways associated with cell proliferation and survival in human mammary epithelial cells. In the present study we demonstrated that BPQs not only induced EGFR tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine phosphorylation of phospholipase C-gamma1 and several signal transducers and activators of transcription (STATs). The effects of BPQs were evaluated in a model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 muM), induced EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC-gamma1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a proposed docking site for PLC-gamma1 on the EGFR. Additionally, we found that BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures. Although the patterns of phosphorylation at EGFR, PLC-gamma1 and STATs were quite similar to those induced by EGF, an important difference between BPQ-mediated signaling of the EGFR was observed. Signaling produced by EGF ligand produced a rapid disappearance of EGFR from the cell surface, whereas BPQ signaling maintained EGFR receptors on the cell membrane. Thus, the results of these studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by EGFR expression, and a prolonged transactivation of EGFR leading to downstream cell signaling pathways.

Peculiarities of carcinogenesis under simultaneous oral administration of benzo(a)pyrene and o-cresol in mice.

PubMed Central

Yanysheva NYa; Balenko, N V; Chernichenko, I A; Babiy, V F

1993-01-01

A modifying influence of ortho-cresol (o-cresol) on the carcinogenic effect of benzo(a)pyrene (BaP) with combined oral administration to CC57Br mice had been found. During simultaneous administration of o-cresol (1 mg) and BaP (1 mg), the incidence of tumors, the multiplicity of tumors, and the degree of malignancy all increased, but the latency was shortened. When o-cresol was administered before or after BaP (in identical doses), the carcinogenic effect was weakened. When o-cresol (10 mg) and BaP (5 mg) were administered simultaneously, the incidence of malignant tumors was similar to controls receiving BaP only (13.8%), indicating inhibition of carcinogenesis. PMID:8143642

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures.

PubMed

Baumeister, Philipp; Reiter, Maximilian; Kleinsasser, Norbert; Matthias, Christoph; Harréus, Ulrich

2009-06-01

Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

Protective Effect of Mulberry (Morus alba L.) Extract against Benzo[a]pyrene Induced Skin Damage through Inhibition of Aryl Hydrocarbon Receptor Signaling.

PubMed

Woo, Hyunju; Lee, JungA; Park, Deokhoon; Jung, Eunsun

2017-12-20

Benzo[a]pyrene (B[a]P), a type of polycyclic aromatic hydrocarbon, is present in the atmosphere surrounding our environment. Although B[a]P is a procarcinogen, enzymatically metabolized benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) could intercalate into DNA to form bulky BPDE-DNA adducts as an ultimate carcinogenic product in human keratinocytes. The aim of this study was to evaluate the protective effect of mulberry extract, purified from the fruit of Morus Alba L., on B[a]P-induced cytotoxicity in human keratinocytes and its mechanisms of action. In this study, we confirmed that B[a]P induced nuclear translocation and the activation of aryl hydrocarbon receptor (AhR) were decreased by pretreatment of mulberry extract. Mulberry extract could decrease DNA damage through the suppression of B[a]P derived DNA adduct formation and restoration of cell cycle retardation at S phase in a dose-dependent manner. Additionally, cyanidin-3-glucoside (C3G), a major active compound of mulberry extract, showed biological activities to protect the cells from B[a]P exposure, similar to the effectivity of the mulberry extract. These results indicated that the inhibitory effect of C3G against B[a]P inducing skin cancer is attributable to repress the AhR signaling pathway.

Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study.

PubMed

Jiang, Cheng-Lan; He, Shui-Wang; Zhang, Yun-Dong; Duan, He-Xian; Huang, Tao; Huang, Yun-Chao; Li, Gao-Feng; Wang, Ping; Ma, Li-Ju; Zhou, Guang-Biao; Cao, Yi

2017-01-03

The lung cancer incidence in the Xuanwei and neighboring region, Yunnan, China, is among the highest in China and is attributed to severe air pollution with high benzo(a)pyrene levels. We systematically and comparatively analyzed DNA methylation alterations at genome and gene levels in Xuanwei lung cancer tissues and cell lines, as well as benzo(a)pyrene-treated cells and mouse samples. We obtained a comprehensive dataset of genome-wide cytosine-phosphate-guanine island methylation in air pollution-related lung cancer samples. Benzo(a)pyrene exposure induced multiple alterations in DNA methylation and in mRNA expressions of DNA methyltransferases and ten-11 translocation proteins; these alterations partially occurred in Xuanwei lung cancer. Furthermore, benzo(a)pyrene-induced DKK2 and EN1 promoter hypermethylation and LPAR2 promoter hypomethylation led to down-regulation and up-regulation of the genes, respectively; the down-regulation of DKK2 and EN1 promoted the cellular proliferation. Thus, DNA methylation alterations induced by benzo(a)pyrene contribute partially to abnormal DNA methylation in air pollution-related lung cancer, and these DNA methylation alterations may affect the development and progression of lung cancer. Additionally, vitamin C and B6 can reduce benzo(a)pyrene-induced DNA methylation alterations and may be used as chemopreventive agents for air pollution-related lung cancer.

EGF-receptor phosphorylation and downstream signaling are activated by benzo[a]pyrene 3,6-quinone and benzo[a]pyrene 1,6-quinone in human mammary epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Fragoso, Lourdes; Melendez, Karla; Hudson, Laurie G.

2009-03-15

Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly mutagenic and carcinogenic metabolites. Previous studies in this laboratory have shown that benzo[a]pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to induce epidermal growth factor receptor (EGFR) cell signaling through the production of reactive oxygen species. Recently, we have reported that BPQs have the potential to induce the expression of genes involved in numerous pathways associated with cell proliferation and survival in human mammary epithelial cells. In the present study we demonstrated that BPQs not only induced EGFR tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine phosphorylation of phospholipase C-{gamma}1 and severalmore » signal transducers and activators of transcription (STATs). The effects of BPQs were evaluated in a model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 {mu}M), induced EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC-{gamma}1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a proposed docking site for PLC-{gamma}1 on the EGFR. Additionally, we found that BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures. Although the patterns of phosphorylation at EGFR, PLC-{gamma}1 and STATs were quite similar to those induced by EGF, an important difference between BPQ-mediated signaling of the EGFR was observed. Signaling produced by EGF ligand produced a rapid disappearance of EGFR from the cell surface, whereas BPQ signaling maintained EGFR receptors on the cell membrane. Thus, the results of these studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by EGFR expression, and a prolonged transactivation of EGFR leading to downstream cell signaling pathways.« less

Linking embryo toxicity with genotoxic responses in the freshwater snail Physa acuta: single exposure to benzo(a)pyrene, fluoxetine, bisphenol A, vinclozolin and exposure to binary mixtures with benzo(a)pyrene.

PubMed

Sánchez-Argüello, Paloma; Aparicio, Natalia; Fernández, Carlos

2012-06-01

Genotoxic effects on fauna after waterborne pollutant exposure have been demonstrated by numerous research programmes. Less effort has been focused on establishing relationship between genotoxicity and long-term responses at higher levels of biological organization. Taking into account that embryos may be more sensitive indicators of reproductive impairment than alterations in fertility, we have developed two assays in multiwell plates to address correlations between embryo toxicity and genotoxicity. The potential teratogenicity was assessed by analyzing abnormal development and mortality of Physa acuta at embryonic stage. Genotoxicity was measured by the micronucleus (MN) test using embryonic cells. Our results showed that linkage between genotoxicity and embryo toxicity depends on mechanisms of action of compounds under study. Embryo toxic responses showed a clear dose-related tendency whereas no clear dose-dependent effect was observed in micronucleus induction. The higher embryo toxicity was produced by benzo(a)pyrene exposure followed by fluoxetine and bisphenol A. Vinclozolin was the lower embryo toxic compound. Binary mixtures with BaP always resulted in higher embryo toxicity than single exposures but antagonistic effects were observed for MN induction. Benzo(a)pyrene produced the higher MN induction at 0.04 mg/L, which also produced clear embryo toxic effects. Fluoxetine did not induce cytogenetic effects but 0.25mg/L altered embryonic development. Bisphenol A significantly reduced hatchability at 0.5mg/L while MN induction appeared with higher treatments than those that start causing teratogenicity. Much higher concentration of vinclozolin (5mg/L) reduced hatchability and induced maximum MN formation. In conclusion, while validating one biomarker of genotoxicity and employing one ecologically relevant effect, we have evaluated the relative sensitivity of a freshwater mollusc for a range of chemicals. The embryo toxicity test is a starting point for the development of a life cycle test with freshwater snails even for undertaking multigeneration studies focused on transgenerational effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Source identification of combustion-related air pollution during an episode and afterwards in winter-time in Istanbul.

PubMed

Kuzu, S Levent

2016-10-11

Conventional air pollutants (PM 10 , CO, NO x ) gradually increased from fall to winter during 2015 in Istanbul. Several air pollution episodes were observed during this period. This study was made in order to determine polycyclic aromatic hydrocarbon (PAH) levels, identify the sources of air pollution, and make toxicity assessment based on Benzo(a)pyrene equivalent concentrations. The sampling took 14 sequential days during winter. High-pressure weather conditions prevailed at the start of the sampling. The conditions were then changed to low-pressure condition towards the end of the sampling. Strong inversion was effective on the onset of the sampling. Strong inversion was effective at the onset of the sampling. A high-volume sampler was used to collect gas and particle phase samples. Total suspended particle concentrations were between 27 and 252 μg m -3 . Sixteen PAH species were investigated. Total (gas + particle) PAH concentrations were between 76.4 and 1280.3 ng m -3 , with an average of 301.4 ng m -3 . Individual PAH concentrations were between not detected (n.d.) and 99.2 ng m -3 in the gaseous phase, and between n.d. and 11.5 ng m -3 in the particle phase. Phenanthrene had the highest share among 16 PAH compounds. Benzo(a)pyrene was not detected in 8 days. On the remaining days, its concentration ranged between 5.5 and 14.8 ng m -3 with an average of 3.7 ng m -3 . Low-molecular-weight PAHs dominated gaseous phase; inversely, high-molecular-weight PAHs dominated particle phase. Possible sources were identified by diagnostic ratios. These ratios suggested that coal combustion and diesel vehicle exhaust emissions had a substantial impact on ambient air quality. Benzo(a)pyrene equivalencies were calculated for each PAH compound in order to make toxicity assessment. Total benzo(a)pyrene equivalencies ranged between 0.4 and 30.0 ng m -3 with an average of 7.2 ng m -3 .

Chlorophyll catalyse the photo-transformation of carcinogenic benzo[a]pyrene in water

PubMed Central

Luo, Lijuan; Lai, Xueying; Chen, Baowei; Lin, Li; Fang, Ling; Tam, Nora F. Y.; Luan, Tiangang

2015-01-01

Algal blooms cause great damage to water quality and aquaculture. However, this study showed that dead algal cells and chlorophyll could accelerate the photo-transformation of benzo[a]pyrene (BaP), a ubiquitous and persistent pollutant with potently mutagenic and carcinogenic toxicities, under visible light irradiation. Chlorophyll was found to be the major active substance in dead algal cells, and generated a high level of singlet oxygen to catalyse the photo-transformation of BaP. According to various BaP metabolites formed, the degradation mechanism was proposed as that chlorophyll in dead algal cells photo-oxidized BaP to quinones via photocatalytic generation of singlet oxygen. The results provided a good insight into the role of chlorophyll in the photo-transformation of organic contaminants and could be a possible remediation strategy of organic pollutants in natural environment. PMID:26239357

Determination of benzo[a]pyrene in edible oils using phase-transfer-catalyst-assisted saponification and supramolecular solvent microextraction coupled to HPLC with fluorescence detection.

PubMed

Wang, Jin; Liu, Laping; Shi, Ludi; Yi, Tingquan; Wen, Yuxia; Wang, Juanli; Liu, Shuhui

2017-01-01

For the analysis of edible oils, saponification is well known as a useful method for eliminating oil matrices. The conventional approach is conducted with alcoholic alkali; it consumes a large volume of organic solvents and impedes the retrieval of analytes by microextraction. In this study, a low-organic-solvent-consuming method has been developed for the analysis of benzo[a]pyrene in edible oils by high-performance liquid chromatography with fluorescence detection. Sample treatment involves aqueous alkaline saponification, assisted by a phase-transfer catalyst, and selective in situ extraction of the analyte with a supramolecular solvent. Comparison of the chromatograms of the oil extracts obtained by different microextraction methods showed that the supramolecular solvent has a better clean-up effect for the unsaponifiable matter from oil matrices. The method offered excellent linearity over a range of 0.03- 5.0 ng mL -1 (r > 0.999). Recovery rates varied from 94 to 102% (RSDs <5.0%). The detection limit and quantification limit were 0.06 and 0.19 μg kg -1 , respectively. The proposed method was applied for the analysis of 52 edible oils collected online in China; the analyte contents of 23 tested oil samples exceeded the maximum limit of 2 μg kg -1 for benzo[a]pyrene set by the Commission Regulation of the European Union. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Contamination of Tea and Tea Infusion with Polycyclic Aromatic Hydrocarbons

PubMed Central

Zachara, Alicja; Gałkowska, Dorota; Juszczak, Lesław

2017-01-01

The aim of this work was to validate the method of determination of polycyclic aromatic hydrocarbons (PAHs), i.e., benzo(a)pyrene and sum of benzo(a)pyrene, benz(a)anthracene, benzo(b)fluoranthene and chrysene in different types of tea, as well as to assess the transfer of these contaminants from tea to tea infusion. The research materials were popular types of black, green, red and white tea. Quantitative and qualitative determination of PAHs was performed by High Performance Liquid Chromatography with fluorimetric detection (HPLC-FLD). The samples were prepared by QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) technique followed by cleaning-up by dispersion solid-phase extraction (d-SPE). Values of limit of detection and limit of quantification obtained in the validation of the method were lower than the respective maximum values given in Commission Regulation (EU) No. 836/2011. The level of contamination of popular teas commercially available on the Polish market with PAHs is similar to that of teas available in other countries, with a very large variation in the concentration of each of the compounds. The highest benzo(a)pyrene and Σ4PAHs contents (209 ± 42 μg/kg and 756 ± 151 μg/kg, respectively) were found for black tea leaves. The transfer of Σ4PAHs from black tea to tea infusions was 0.48%, while it was 1.55–1.72% for red, white and green teas. PMID:29283369

Multiphoton spectral analysis of benzo[a]pyrene uptake and metabolism in a rat liver cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barhoumi, Rola, E-mail: rmouneimne@cvm.tamu.edu; Mouneimne, Youssef; Ramos, Ernesto

2011-05-15

Dynamic analysis of the uptake and metabolism of polycyclic aromatic hydrocarbons (PAHs) and their metabolites within live cells in real time has the potential to provide novel insights into genotoxic and non-genotoxic mechanisms of cellular injury caused by PAHs. The present work, combining the use of metabolite spectra generated from metabolite standards using multiphoton spectral analysis and an 'advanced unmixing process', identifies and quantifies the uptake, partitioning, and metabolite formation of one of the most important PAHs (benzo[a]pyrene, BaP) in viable cultured rat liver cells over a period of 24 h. The application of the advanced unmixing process resulted inmore » the simultaneous identification of 8 metabolites in live cells at any single time. The accuracy of this unmixing process was verified using specific microsomal epoxide hydrolase inhibitors, glucuronidation and sulfation inhibitors as well as several mixtures of metabolite standards. Our findings prove that the two-photon microscopy imaging surpasses the conventional fluorescence imaging techniques and the unmixing process is a mathematical technique that seems applicable to the analysis of BaP metabolites in living cells especially for analysis of changes of the ultimate carcinogen benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide. Therefore, the combination of the two-photon acquisition with the unmixing process should provide important insights into the cellular and molecular mechanisms by which BaP and other PAHs alter cellular homeostasis.« less

Preliminary Feasibility Study of Benzo(a)Pyrene Oxidative Degradation by Fenton Treatment

PubMed Central

Homem, Vera; Dias, Zélia; Santos, Lúcia; Alves, Arminda

2009-01-01

Polycyclic aromatic hydrocarbons (PAHs) are considered priority compounds due to their toxic and carcinogenic nature. The concern about water contamination and the consequent human exposure has encouraged the development of new methods for PAHs removal. The purpose of this work was to study the feasibility of a degradation process of benzo(a)pyrene (BaP) in aqueous matrices by oxidation with Fenton reagent. A laboratory unit was designed to optimize the factors which may influence the process: pH (3.5 to 6.0), temperature (30 to 70°C), H2O2 (20 to 150 mg L−1), Fe2+ concentration (2.75 to 5.50 mg L−1), and the initial concentration of the pollutant (10 to 100 μg L−1). The pH did not influence significantly the results in the range studied. An increase in temperature from 30 to 70°C improved the removal efficiency from 90% to 100%. The same effect was observed for ferrous ion concentrations from 2.75 to 5.50 mg L−1 (increase from 78% to 100% removal). The H2O2 concentration played a double role during the process: from 20 to 50 mg L−1 an increase in the removal efficiency was achieved, but for higher concentrations (>50 mg L−1) the degradation is lower. This study proved that the degradation of benzo(a)pyrene by Fenton's reagent is a viable process. PMID:19936125

Biodegradation of polycyclic aromatic hydrocarbons by new isolates of white rot fungi.

PubMed Central

Field, J A; de Jong, E; Feijoo Costa, G; de Bont, J A

1992-01-01

Eight rapid Poly R-478 dye-decolorizing isolates from The Netherlands were screened in this study for the biodegradation of polycyclic aromatic hydrocarbons (PAH) supplied at 10 mg liter(-1). Several well-known ligninolytic culture collection strains, Phanerochaete chrysosporium BKM-F-1767, Trametes versicolor Paprican 52, and Bjerkandera adusta CBS 595.78 were tested in parallel. All of the strains significantly removed anthracene, and nine of the strains significantly removed benzo(a)pyrene beyond the limited losses observed in sterile liquid and HgCl2-poisoned fungus controls. One of the new isolates, Bjerkandera sp. strain Bos 55, was the best degrader of both anthracene and benzo(a)pyrene, removing 99.2 and 83.1% of these compounds after 28 days, respectively. Half of the strains, exemplified by strains of the genera Bjerkandera and Phanerochaete, converted anthracene to anthraquinone, which was found to be a dead-end metabolite, in high yields. The extracellular fluids of selected strains were shown to be implicated in this conversion. In contrast, four Trametes strains removed anthracene without significant accumulation of the quinone. The ability of Trametes strains to degrade anthraquinone was confirmed in this study. None of the strains accumulated PAH quinones during benzo(a)pyrene degradation. Biodegradation of PAH by the various strains was highly correlated to the rate by which they decolorized Poly R-478 dye, demonstrating that ligninolytic indicators are useful in screening for promising PAH-degrading white rot fungal strains. PMID:1637159

Investigating Cancer Clusters, Brooks AFB, Texas

DTIC Science & Technology

1990-10-01

based dyes Bladder Benzotrichloride Lung? Cadmium and related compounds Prostate, lung Chloroform Bladder, brain, kidney, lymphoma? Chlorophenols Soft...Dioxine) Vinyl chloride Lung Acrylonitrile Aldrin/dieldrin Arsenic Asbestos Benzo[a]pyrene Benzotrichloride Beryllium Cadmium Chloroprene Chromium Coal

40 CFR 421.26 - Pretreatment standards for new sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... .077 Fluoride 12.440 5.518 (c) Subpart B—Anode Bake Plant Wet Air Pollution Control. PSNS Pollutant or... anodes baked Benzo(a)pyrene .000 Nickel .000 .000 Fluoride .000 .000 (d) Subpart B—Cathode Reprocessing...

40 CFR 421.24 - Standards of performance for new sources.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) Subpart B—Anode Bake Plant Wet Air Pollution Control. NSPS Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kg (pound per million pounds) of anodes baked Benzo(a)pyrene...

40 CFR 421.26 - Pretreatment standards for new sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... .077 Fluoride 12.440 5.518 (c) Subpart B—Anode Bake Plant Wet Air Pollution Control. PSNS Pollutant or... anodes baked Benzo(a)pyrene .000 Nickel .000 .000 Fluoride .000 .000 (d) Subpart B—Cathode Reprocessing...

40 CFR 421.26 - Pretreatment standards for new sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... .077 Fluoride 12.440 5.518 (c) Subpart B—Anode Bake Plant Wet Air Pollution Control. PSNS Pollutant or... anodes baked Benzo(a)pyrene .000 Nickel .000 .000 Fluoride .000 .000 (d) Subpart B—Cathode Reprocessing...

40 CFR 421.24 - Standards of performance for new sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) Subpart B—Anode Bake Plant Wet Air Pollution Control. NSPS Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kg (pound per million pounds) of anodes baked Benzo(a)pyrene...

40 CFR 421.26 - Pretreatment standards for new sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... .077 Fluoride 12.440 5.518 (c) Subpart B—Anode Bake Plant Wet Air Pollution Control. PSNS Pollutant or... anodes baked Benzo(a)pyrene .000 Nickel .000 .000 Fluoride .000 .000 (d) Subpart B—Cathode Reprocessing...

40 CFR 421.24 - Standards of performance for new sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) Subpart B—Anode Bake Plant Wet Air Pollution Control. NSPS Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kg (pound per million pounds) of anodes baked Benzo(a)pyrene...

40 CFR 421.26 - Pretreatment standards for new sources.

Code of Federal Regulations, 2014 CFR

2014-07-01

... .077 Fluoride 12.440 5.518 (c) Subpart B—Anode Bake Plant Wet Air Pollution Control. PSNS Pollutant or... anodes baked Benzo(a)pyrene .000 Nickel .000 .000 Fluoride .000 .000 (d) Subpart B—Cathode Reprocessing...

40 CFR 421.24 - Standards of performance for new sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Subpart B—Anode Bake Plant Wet Air Pollution Control. NSPS Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kg (pound per million pounds) of anodes baked Benzo(a)pyrene...

Polycyclic aromatic hydrocarbon levels and risk assessment for food from service facilities in Korea.

PubMed

Park, Shin-Woong; Jeong, Jun-Hyun; Her, Jae-Young; Kim, Mina K; Lee, Kwang-Geun

2017-06-01

In this study, levels of benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene (BaP), dibenzo[a,h]anthracene, benzo[g,h,i]perylene and indeno[1,2,3-c,d]pyrene in 412 food items collected from food service facilities in Korea were analysed. The concentrations of the eight polycyclic aromatic hydrocarbons (PAHs) ranged 0.13-0.48 μg/kg. The concentrations of benzo[a]pyrene in all food samples were <1 μg/kg, which is the lowest maximum limit in foods regulated by European Union legislation. PAH contents were employed to conduct exposure and risk assessment. The chronic daily intake of PAHs from 412 food samples was 5.48 × 10 -6 -4.70 ×x 10 -4  µg-TEQ BaP /kg/day with margins of exposure of 1.04 × 10 9 -1.16 × 10 11 .

Rapid communication: effects of tobacco processing on the quantity of benzo[a]pyrene in mainstream smoke.

PubMed

Martin, Lin Alicia; Byrd, Sherell K; Milofsky, Robert E

2003-07-25

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon produced during incomplete combustion of organic compounds and is one of the more carcinogenic PAHs detected in tobacco smoke. Addition of organic compounds during tobacco processing increases the likelihood of finding elevated concentrations of BaP in mainstream smoke when compared to smoke from unprocessed tobacco. To test this hypothesis, the tobacco from Marlboro "Red" (processed) cigarettes and nonprocessed Burley tobacco leaf cigarettes was combusted and the resulting combustion products were collected onto glass fiber filter pads. The quantity of BaP in the tobacco tar extracted from the pads was measured using reversed-phase liquid chromatography with fluorescence detection. The concentration of BaP in the processed tobacco smoke was significantly higher than in unprocessed tobacco smoke. These results suggest that compounds added during tobacco processing increase the concentrations of BaP and therefore the carcinogenic potential of cigarettes.

Pilot Metabolome-Wide Association Study of Benzo(a)pyrene in Serum from Military Personnel

PubMed Central

Walker, Douglas I.; Pennell, Kurt D.; Uppal, Karan; Xia, Xiaoyan; Hopke, Philip K.; Utell, Mark J.; Phipps, Richard P.; Sime, Patricia J.; Rohrbeck, Patricia; Mallon, COL Timothy M.; Jones, Dean P.

2016-01-01

Objective A pilot study was conducted to test the feasibility of using Department of Defense Serum Repository (DoDSR) samples to study health and exposure-related effects. Methods Thirty unidentified human serum samples were obtained from the DoDSR and analyzed for normal serum metabolites with high-resolution mass spectrometry and serum levels of free benzo(a)pyrene (BaP) by gas chromatography-mass spectrometry. Metabolic associations with BaP were determined using a metabolome wide association study (MWAS) and metabolic pathway enrichment. Results The serum analysis detected normal ranges of glucose, selected amino acids, fatty acids, and creatinine. Free BaP was detected in a broad concentration range. MWAS of BaP showed associations with lipids, fatty acids, and sulfur amino acid metabolic pathways. Conclusion The results show the DoDSR samples are of sufficient quality for chemical profiling of DoD personnel. PMID:27501104

Pilot Metabolome-Wide Association Study of Benzo(a)pyrene in Serum From Military Personnel.

PubMed

Walker, Douglas I; Pennell, Kurt D; Uppal, Karan; Xia, Xiaoyan; Hopke, Philip K; Utell, Mark J; Phipps, Richard P; Sime, Patricia J; Rohrbeck, Patricia; Mallon, Col Timothy M; Jones, Dean P

2016-08-01

A pilot study was conducted to test the feasibility of using Department of Defense Serum Repository (DoDSR) samples to study health and exposure-related effects. Thirty unidentified human serum samples were obtained from the DoDSR and analyzed for normal serum metabolites with high-resolution mass spectrometry and serum levels of free benzo(a)pyrene (BaP) by gas chromatography-mass spectrometry. Metabolic associations with BaP were determined using a metabolome-wide association study (MWAS) and metabolic pathway enrichment. The serum analysis detected normal ranges of glucose, selected amino acids, fatty acids, and creatinine. Free BaP was detected in a broad concentration range. MWAS of BaP showed associations with lipids, fatty acids, and sulfur amino acid metabolic pathways. The results show that the DoDSR samples are of sufficient quality for chemical profiling of DoD personnel.

Carcinogenic agents in snuff.

PubMed

Hoffmann, D; Harley, N H; Fisenne, I; Adams, J D; Brunnemann, K D

1986-03-01

The oral use of snuff has been associated with an increased-risk for cancer of the oral cavity and pharynx. The five most popular U.S. snuff brands were analyzed for alkaloids, volatile and tobacco-specific N-nitrosamines (TSNA), benzo[a]pyrene (CAS: 50-32-8), and polonium-210. The carcinogenic TSNA in the five snuff brands ranged from 9,600 to 289,000 ppb. These concentrations exceed the nitrosamine concentrations of other consumer products by at least 2 orders of magnitude. Polonium amounted to 0.16-1.22 pCi/g dry snuff. Trace amounts of benzo[a]pyrene (0.1-63 ppb) were indicative of contamination of the tobacco with thermal degradation products, probably due to fire curing or flue curing. The findings from this study, the biologic activity of snuff in animal models, and the epidemiologic studies on snuff use and oral cancer strongly suggest the need for reduction of carcinogens and especially of nitrosamines and polonium-210 in snuff.

Polynuclear aromatic hydrocarbon analysis using the synchronous scanning luminoscope

NASA Astrophysics Data System (ADS)

Hyfantis, George J., Jr.; Teglas, Matthew S.; Wilbourn, Robert G.

2001-02-01

12 The Synchronous Scanning Luminoscope (SSL) is a field- portable, synchronous luminescence spectrofluorometer that was developed for on-site analysis of contaminated soil and ground water. The SSL is capable of quantitative analysis of total polynuclear aromatic hydrocarbons (PAHs) using phosphorescence and fluorescence techniques with a high correlation to laboratory data as illustrated by this study. The SSL is also capable of generating benzo(a)pyrene equivalency results, based on seven carcinogenic PAHs and Navy risk numbers, with a high correlation to laboratory data as illustrated by this study. These techniques allow rapid field assessments of total PAHs and benzo(a)pyrene equivalent concentrations. The Luminoscope is capable of detecting total PAHs to the parts per billion range. This paper describes standard field methods for using the SSL and describes the results of field/laboratory testing of PAHs. SSL results from two different hazardous waste sites are discussed.

Measurement of some potentially hazardous materials in the atmosphere of rubber factories.

PubMed Central

Nutt, A

1976-01-01

Two separate topics of work are outlined: methods for the measurement of chlorinated monomers in PVC and polychloroprene, and also methods for the measurement of these materials in factory air. Typical results which have been obtained in supplies of raw materials, in finished products, and in the working atmosphere at manufacturing operations are given. The second topic concerns the measurement of benzo[a]pyrene in the atmosphere of a tire manufacturing plant. This material is present in trace quantities in the mineral oils and carbon blacks used by the industry. The atmospheric concentrations present at various processes in this plant were measured on a daily basis over a period of two years, and the results obtained compared with results taken concurrently from an outside air station. It is shown that no significant quantities of benzo[a]pyrene are produced by tire manufacturing operations. Images FIGURE 1. FIGURE 2. FIGURE 4. FIGURE 5. PMID:1026396

Digestive determinants of benzo[a]pyrene and phenanthrene bioaccumulation by a deposit-feeding polychaete

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penry, D.L.; Weston, D.P.

1998-11-01

The uptake of hydrophobic contaminants from ingested sediment can contribute significantly to body burdens of deposit feeders, and feeding behavior and digestive physiology can play important roles in bioaccumulation. The authors examined the uptake of polycyclic aromatic hydrocarbons (PAHs) by the deposit-feeding polychaete Abarenicola pacifica in experiments in which worms were first acclimated to low or high organic carbon sediments with 0.08 or 0.45% total organic carbon, respectively and then transferred to low or high organic carbon test sediments contaminated with radiolabeled phenanthrene or benzo[a]pyrene. Ingestion rate was measurements are essential in many types of bioaccumulation studies because differences inmore » ingestion rates between sediment types may confound some traditional measures of bioavailability. Physiological acclimation to the low or high organic carbon sediments did not appear to affect PAH uptake from the test sediments, but acclimation did affect biotransformation capabilities, particularly for phenanthrene.« less

Liquid chromatographic determination of benzo(a)pyrene in total particulate matter of cigarette smoke

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomkins, B.A.; Jenkins, R.A.; Griest, W.H.

The benzo(a)pyrene (BaP) delivery of reference and commercially available tobacco cigarettes, as well as reference and placebo marijuana cigarettes, is determined using a sequential liquid chromatographic/liquid chromatographic procedure. The total particulate matter of sample cigarette smoke is collected using a Cambridge filter pad, which is ultrasonically extracted with acetone. The resulting extract is filtered, then fractionated using semipreparative-scale normal phase liquid chromatography (LC). Quantitative determination is achieved using analytical-scale reverse phase LC equipped with a fluorescence detector. The method is precise (+/- 10-15% relative standard deviation) and yields 85% or better BaP recovery at the ng/cig. level. A single padmore » may be analyzed in 8 person-hours, while a more typical lot of 12 pads (6 pads each for 2 cigarette brands) may be analyzed in 10 person-days.« less

Development and Uses of Offline and Web-Searchable Metabolism Databases - The Case of Benzo[a]pyrene.

PubMed

Rendic, Slobodan P; Guengerich, Frederick P

2018-01-01

The present work describes development of offline and web-searchable metabolism databases for drugs, other chemicals, and physiological compounds using human and model species, prompted by the large amount of data published after year 1990. The intent was to provide a rapid and accurate approach to published data to be applied both in science and to assist therapy. Searches for the data were done using the Pub Med database, accessing the Medline database of references and abstracts. In addition, data presented at scientific conferences (e.g., ISSX conferences) are included covering the publishing period beginning with the year 1976. Application of the data is illustrated by the properties of benzo[a]pyrene (B[a]P) and its metabolites. Analysis show higher activity of P450 1A1 for activation of the (-)- isomer of trans-B[a]P-7,8-diol, while P4501B1 exerts higher activity for the (+)- isomer. P450 1A2 showed equally low activity in the metabolic activation of both isomers. The information collected in the databases is applicable in prediction of metabolic drug-drug and/or drug-chemical interactions in clinical and environmental studies. The data on the metabolism of searched compound (exemplified by benzo[a]pyrene and its metabolites) also indicate toxicological properties of the products of specific reactions. The offline and web-searchable databases had wide range of applications (e.g. computer assisted drug design and development, optimization of clinical therapy, toxicological applications) and adjustment in everyday life styles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Transfer of benzo[a]pyrene from microplastics to Artemia nauplii and further to zebrafish via a trophic food web experiment: CYP1A induction and visual tracking of persistent organic pollutants.

PubMed

Batel, Annika; Linti, Frederic; Scherer, Martina; Erdinger, Lothar; Braunbeck, Thomas

2016-07-01

The uptake of microplastic particles and the transfer of potential harmful substances along with microplastics has been studied in a variety of organisms, especially invertebrates. However, the potential accumulation of very small microplastic particles along food webs ending with vertebrate models has not been investigated so far. Therefore, a simple artificial food chain with Artemia sp. nauplii and zebrafish (Danio rerio) was established to analyze the transfer of microplastic particles and associated persistent organic pollutants (POPs) between different trophic levels. Very small (1-20 μm) microplastic particles accumulated in Artemia nauplii and were subsequently transferred to fish. Virgin particles not loaded with POPs did not cause any observable physical harm in the intestinal tracts of zebrafish, although parts of the particles were retained within the mucus of intestinal villi and might even have been taken up by epithelial cells. The transfer of associated POPs was tested with the polycyclic aromatic hydrocarbon benzo[a]pyrene and an ethoxyresorufin-O-deethylase (EROD) assay for CYP1A induction in zebrafish liver as well as via fluorescence analyses. Whereas a significant induction in the EROD assay could not be shown, because of high individual variation and low sensitivity regarding substance concentration, the fluorescence tracking of benzo[a]pyrene indicates that food-borne microplastic-associated POPs may actually desorb in the intestine of fish and are thus transferred to the intestinal epithelium and liver. Environ Toxicol Chem 2016;35:1656-1666. © 2016 SETAC. © 2016 SETAC.

Effects of soil amendment with different carbon sources and other factors on the bioremediation of an aged PAH-contaminated soil.

PubMed

Teng, Ying; Luo, Yongming; Ping, Lifeng; Zou, Dexun; Li, Zhengao; Christie, Peter

2010-04-01

Carbon supplementation, soil moisture and soil aeration are believed to enhance in situ bioremediation of PAH-contaminated soils by stimulating the growth of indigenous microorganisms. However, the effects of added carbon and nitrogen together with soil moisture and soil aeration on the dissipation of PAHs and on associated microbial counts have yet to be fully assessed. In this study the effects on bioremediation of carbon source, carbon-to-nitrogen ratio, soil moisture and aeration on an aged PAH-contaminated agricultural soil were studied in microcosms over a 90-day period. Additions of starch, glucose and sodium succinate increased soil bacterial and fungal counts and accelerated the dissipation of phenanthrene and benzo(a)pyrene in soil. Decreases in phenanthrene and benzo(a)pyrene concentrations were effective in soil supplemented with glucose and sodium succinate (both 0.2 g C kg(-1) dry soil) and starch (1.0 g C kg(-1) dry soil). The bioremediation effect at a C/N ratio of 10:1 was significantly higher (P < 0.05) than at a C/N of either 25:1 or 40:1. Soil microbial counts and PAH dissipation were lower in the submerged soil but soil aeration increased bacterial and fungal counts, enhanced indigenous microbial metabolic activities, and accelerated the natural degradation of phenanthrene and benzo(a)pyrene. The results suggest that optimizing carbon source, C/N ratio, soil moisture and aeration conditions may be a feasible remediation strategy in certain PAH contaminated soils with large active microbial populations.

Exposure to benzo[a]pyrene of Hepatic Cytochrome P450 Reductase Null (HRN) and P450 Reductase Conditional Null (RCN) mice: Detection of benzo[a]pyrene diol epoxide-DNA adducts by immunohistochemistry and 32P-postlabelling.

PubMed

Arlt, Volker M; Poirier, Miriam C; Sykes, Sarah E; John, Kaarthik; Moserova, Michaela; Stiborova, Marie; Wolf, C Roland; Henderson, Colin J; Phillips, David H

2012-09-03

Benzo[a]pyrene (BaP) is a widespread environmental carcinogen activated by cytochrome P450 (P450) enzymes. In Hepatic P450 Reductase Null (HRN) and Reductase Conditional Null (RCN) mice, P450 oxidoreductase (Por) is deleted specifically in hepatocytes, resulting in the loss of essentially all hepatic P450 function. Treatment of HRN mice with a single i.p. or oral dose of BaP (12.5 or 125mg/kg body weight) resulted in higher DNA adduct levels in liver (up to 10-fold) than in wild-type (WT) mice, indicating that hepatic P450s appear to be more important for BaP detoxification in vivo. Similar results were obtained in RCN mice. We tested whether differences between hepatocytes and non-hepatocytes in P450 activity may underlie the increased liver BaP-DNA binding in HRN mice. Cellular localisation by immunohistochemistry of BaP-DNA adducts showed that HRN mice have ample capacity for formation of BaP-DNA adducts in liver, indicating that the metabolic process does not result in the generation of a reactive species different from that formed in WT mice. However, increased protein expression of cytochrome b(5) in hepatic microsomes of HRN relative to WT mice suggests that cytochrome b(5) may modulate the P450-mediated bioactivation of BaP in HRN mice, partially substituting the function of Por. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish.

PubMed

Knecht, Andrea L; Truong, Lisa; Marvel, Skylar W; Reif, David M; Garcia, Abraham; Lu, Catherine; Simonich, Michael T; Teeguarden, Justin G; Tanguay, Robert L

2017-08-15

Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10μM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling

PubMed Central

Campbell, Jerry; Franzen, Allison; Van Landingham, Cynthia; Lumpkin, Michael; Crowell, Susan; Meredith, Clive; Loccisano, Anne; Gentry, Robinan; Clewell, Harvey

2016-01-01

Abstract Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. PMID:27569524

Health Effects Assessment for Benzo[a]pyrene

EPA Science Inventory

This final report represents a brief, quantitatively oriented scientific summary of health effects data. It was developed by the Environmental Criteria and Assessment Office to assist the Office of Emergency and Remedial Response in establishing chemical-specific health-related g...

Two-liquid-phase slurry bioreactors to enhance the degradation of high-molecular-weight polycyclic aromatic hydrocarbons in soil.

PubMed

Villemur, R; Déziel, E; Benachenhou, A; Marcoux, J; Gauthier, E; Lépine, F; Beaudet, R; Comeau, Y

2000-01-01

High-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) are pollutants that persist in the environment due to their low solubility in water and their sequestration by soil and sediments. The addition of a water-immiscible, nonbiodegradable, and biocompatible liquid, silicone oil, to a soil slurry was studied to promote the desorption of PAHs from soil and to increase their bioavailability. First, the transfer into silicone oil of phenanthrene, pyrene, chrysene, and benzo[a]pyrene added to a sterilized soil (sandy soil with 0.65% total volatile solids) was measured for 4 days in three two-liquid-phase (TLP) slurry systems each containing 30% (w/v) soil but different volumes of silicone oil (2.5%, 7.5%, and 15% [v/v]). Except for chrysene, a high percentage of these PAHs was transferred from soil to silicone oil in the TLP slurry system containing 15% silicone oil. Rapid PAH transfer occurred during the first 8 h, probably resulting from the extraction of nonsolubilized and of poorly sorbed PAHs. This was followed by a period in which a slower but constant transfer occurred, suggesting extraction of more tightly bound PAHs. Second, a HMW PAH-degrading consortium was enriched in a TLP slurry system with a microbial population isolated from a creosote-contaminated soil. This consortium was then added to three other TLP slurry systems each containing 30% (w/v) sterilized soil that had been artificially contaminated with pyrene, chrysene, and benzo[a]pyrene, but different volumes of silicone oil (10%, 20%, and 30% [v/v]). The resulting TLP slurry bioreactors were much more efficient than the control slurry bioreactor containing the same contaminated soil but no oil phase. In the TLP slurry bioreactor containing 30% silicone oil, the rate of pyrene degradation was 19 mg L(-)(1) day(-)(1) and no pyrene was detected after 4 days. The degradation rates of chrysene and benzo[a]pyrene in the 30% TLP slurry bioreactor were, respectively, 3.5 and 0.94 mg L(-)(1) day(-)(1). Low degradation of pyrene and no significant degradation of chrysene and benzo[a]pyrene occurred in the slurry bioreactor. This is the first report in which a TLP system was combined with a slurry system to improve the biodegradation of PAHs in soil.

Benzo[a]pyrene (BaP)

Integrated Risk Information System (IRIS)

EPA / 635 / R - 17 / 003Fc www.epa.gov / iris Toxicological Review of Benzo [ a ] pyrene Executive Summary [ CASRN 50 - 32 - 8 ] January 2017 Integrated Risk Information System National Center for Environmental Assessment Office of Research and Development U.S . Environmental Protection Agency Washi

HISTORICAL MONITORING OF BIOMARKERS OF EXPOSURE OF BROWN BULLHEAD

EPA Science Inventory

Biomarkers of exposure to chemical contamination, benzo(a)pyrene (BAP) and naphthalene (NAPH) type metabolites were measured in brown bullhead from a heavily polycyclic aromatic hydrocarbon (PAH) contaminated section of the Black River, Ohio during and immediately after remedial ...

Polycyclic aromatic hydrocarbons in a bakery indoor air: trends, dynamics, and dispersion.

PubMed

Ielpo, Pierina; Taurino, Maria Rosaria; Buccolieri, Riccardo; Placentino, Claudia Marcella; Gallone, Francesco; Ancona, Valeria; Di Sabatino, Silvana

2018-02-27

Indoor air pollution assessment in work environments remains challenging due to a combination of logistic reasons and availability of costly instrumentation for data acquisition and post-processing. Existing literature focuses on energy production environments, hospitals, and less so on food production spaces. Studies on indoor air quality in bakeries are scarce or even absent. Motivated by this, the present study investigates indoor air quality in a bakery located in Bari province in South Italy, using a combination of approaches including analytical chemistry analyses and computational fluid dynamics to reconstruct the air ventilation in response to air temperature gradients within the working environment. PM 2.5 indoor samplings were collected every 6 h from 7 to 19 April 2013 in the proximity of two bakery ovens powered by gas and wood, respectively. For each sampling day, 4 PM 2.5 samples were collected: from 3:00 to 9:00 h (first), from 9:00 to 13:30 h (second), from 14:00 to 21:00 h (third), and from 21:00 to 3:00 h (fourth). In total, 40 samples were collected. On each sample, several polycyclic aromatic hydrocarbons (PAHs) were determined such as benzo[a]anthracene (228), benzo[b]fluoranthene (252), benzo[k]fluoranthene (252), benzo[a]pyrene (252), benzo[g,h,i]perylene (276), indeno[1,2,3-cd]pyrene (276), and dibenzo[a,h]anthracene (278), the main compounds of 16 priority US Environmental Protection Agency (US-EPA) PAHs in particulate phase. The PAH mean concentrations showed higher values during the first (from 3:00 to 9:00 h) and fourth (from 21:00 to 3:00 h) sampling intervals than the other two with benzo[a]pyrene mean values exceeding the Italian law limit of 1 ng/m 3 . Taking into account benzo[a]pyrene mean concentration for the first interval and the first plus the second one, which are the hours with the largest working activity, we have estimated that the baker and co-workers are exposed to a cancer risk of 4.3 × 10 -7 and 5.8 × 10 -7 , respectively (these values are lower than US-EPA recommended guideline of 10 -6 ). Our study was complemented by numerical analyses using state-of-the-art computational fluid dynamics to reconstruct at high resolution air movement from the various working places, i.e., the bakery and the selling area which were connected via a door. The numerical simulations were possible given that surface temperature using infrared thermography as well as air temperature was continuously recorded throughout the sampling acquisition. The use of this approach allowed us to estimate the transport and diffusion of benzo[a]pyrene from one area to the other thus complementing the point sampling information. Computational fluid dynamic simulation results confirm the presence of benzo[a]pyrene in the laboratory as obtained from the measurements and suggests its presence in the sales' area of the bakery with concentrations similar those found in the laboratory.

RELATIONSHIP BETWEEN METABOLISM AND BIOACCUMULATION OF BENZO[A]PYRENE IN BENTHIC INVERTEBRATES

EPA Science Inventory

The potential influence of polycyclic aromatic hydrocarbon (PAH) metabolism on bioaccumulation is well accepted, but rarely has been examined in many species of benthic invertebrates that commonly are found in contaminated sediments, or used in bioaccumulation or toxicity tests. ...

The influence of smoking in traditional conditions on content of polycyclic aromatic hydrocarbons in Petrovská klobása

NASA Astrophysics Data System (ADS)

Škaljac, S.; Petrović, Lj; Jokanović, M.; Tomović, V.; Tasić, T.; Ivić, M.; Šojić, B.; Ikonić, P.; Džinić, N.

2017-09-01

The aim of this study was to determine the content of 13 polycyclic aromatic hydrocarbons (acenaphthylene, fluorene, phenanthrene, anthracene, pyrene, benz[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, dibenz[a,h]anthracene and benzo[ghi]perylene) the from Environmental Protection Agency list (US-EPA PAH) in traditional dry fermented sausage Petrovská klobása. Sausages were smoked in traditional conditions and samples for analyses were taken on day 0 of production (0), at the end of drying (T1) and at the end of the storage period (T2). The highest total content of 13 US-EPA PAHs was determined in sausages at the end of the storage period (73.5 μg/kg). Phenanthrene was the most abundant of the PAHs in all examined sausage samples (0-4.90 μg/kg T1-18.0 μg/kg and T2-26.3 μg/kg). Benzo[a]pyrene, with a maximum allowed content in smoked meat products of 2 µg/kg (EC No. 835/2011), was below the limit of detection in all examined samples. Also, PAH4 (the total content of benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene) with a maximum allowed content in smoked meat products of 12 µg/kg (EC No. 835/2011), was below the limit of detection in all examined sausage samples. According to the results obtained in this study, and in regard to the European regulation on PAHs content, the dry fermented sausage Petrovská klobása, smoked in traditional conditions, was safe for consumers.

Presence of Polycyclic Aromatic Hydrocarbons in Rubber Packaging Materials and in Parenteral Formulations Stored in Bottles With Rubber Stoppers.

PubMed

Bohrer, Denise; Viana, Carine; Barichello, Marcia M; de Moura, Juliane F; de Carvalho, Leandro M; Nascimento, Paulo C

2017-08-01

Rubber closures are the primary packaging material for sterile preparations intended for repeated use. Important features of rubber closures are achieved after additives are added to the elastomeric material that compounds the rubber. Among these additives is carbon black. Because of its origin, carbon black may contain polycyclic aromatic hydrocarbons (PAHs). The U.S. Environmental Protection Agency has identified 16 priority PAHs on the basis of concerns that they cause or might cause cancer in animals and humans. Regulatory agencies impose carbon black purity specifications based on limits for total PAHs (0.5 mg/kg) and benzo[a]pyrene (5 μg/kg) or benzo[a]pyrene only (250 μg/kg). PAHs in rubber packaging used for pharmaceutical formulations and in parenteral products stored in containers with rubber stoppers were investigated. To this end, the method proposed by the National Institute for Occupational Safety and Health-based on high-performance liquid chromatography with ultraviolet and fluorescence detection-was adapted to determine the levels of PAHs in rubber stoppers (gray and red) and in lipid emulsions and amino acid solutions stored in bottles with rubber stoppers. The rubber materials were shown to contain 12 PAHs, in concentrations ranging from 0.25-3.31 µg/g. Only 1 of 18 samples (11 amino acid solutions and 7 lipid emulsions) was uncontaminated. The most prevalent contaminants were pyrene, benzo[a]pyrene, and fluoranthene. The total PAH concentrations in the samples ranged from 0.11-5.96 µg/mL. Components of parenteral nutrition may be contaminated with PAHs, and rubber stoppers represent a potential source of these contaminants.

Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility.

PubMed

Hu, Ting; Pan, Qinxin; Andrew, Angeline S; Langer, Jillian M; Cole, Michael D; Tomlinson, Craig R; Karagas, Margaret R; Moore, Jason H

2014-04-11

Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility. To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types. The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies.

Benzo(a)pyrene parallel measurements in PM1 and PM2.5 in the coastal zone of the Gulf of Gdansk (Baltic Sea) in the heating and non-heating seasons.

PubMed

Lewandowska, Anita Urszula; Staniszewska, Marta; Witkowska, Agnieszka; Machuta, Magdalena; Falkowska, Lucyna

2018-05-05

Parallel measurements of PM 1 and PM 2.5 aerosols were conducted in the urbanized coastal zone of the southern Baltic Sea. The main aim of the research was to assess and determine annual, seasonal (heating and non-heating), and daily concentration variability of benzo(a)pyrene in aerosols, these being the most dangerous constituents to human health. The average annual concentration of benzo(a)pyrene (B(a)P) was equal to 2.6 ng·m -3 in PM 1 and 4.6 ng·m -3 in PM 2.5 , and both values were several times higher than the level of 1 ng·m -3 which was set out in the CAFE Directive. High mean daily concentrations of B(a)P persisted for 50 and 65% of the study period in PM1 and PM2.5, respectively. In order to determine the sources of B(a)P in both aerosol fractions, organic (OC) and elemental (EC) carbon concentrations were examined. The highest concentrations of all carbon species were reported during the heating season under local or regional land advection and at low air temperatures. The origin of pollutants was the same and was primarily related to the combustion of fossil fuels in the communal-utility sector. During the non-heating period, the role of transportation, both land and marine, increased and may have been significant in creating higher concentrations of carbon compounds in PM 1 and PM 2.5 . Regardless of the size of the aerosol fractions, B(a)P loads introduced into the Baltic coastal zone were several times higher during the heating period compared to the non-heating season. Graphical abstract ᅟ.

COMBUSTION CONTROL OF ORGANIC EMISSIONS FROM MUNICIPAL WASTE COMBUSTORS

EPA Science Inventory

More than two decades ago, researchers identified benzo(a)pyrene and other organic species in the emissions from incineration of solid waste. Chlorinated dibenzo-p-dioxins and-furans (CDD/CDF) were first detected in municipal waste combustor (MWC) emissions in 1977. Since then, C...

Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts.

PubMed Central

Newman, M J; Light, B A; Weston, A; Tollurud, D; Clark, J L; Mann, D L; Blackmon, J P; Harris, C C

1988-01-01

The presence of serum antibodies to the diol-epoxide DNA adducts of representative polycyclic aromatic hydrocarbons (PAH), chrysene, benz[a]anthracene and benzo[a]pyrene, was determined by ELISA using serum samples obtained from normal healthy individuals. Antibodies that reacted against PAH adducted-DNA, but not against PAH-adducted protein, were found in the serum of approximately 40% of the test individuals. Specificity analysis of the antibodies demonstrated that serological cross-reactions between the benzo[a]pyrene and the chrysene diol-epoxide adducts were present. Similar cross-reactivity between the benz[a]anthracene and the chrysene adducts was observed. Sera containing antibodies that were apparently specific for each of the three PAH-DNA adducts were also identified. The presence of antibodies to PAH-DNA adducts indicates both past exposure to these carcinogenic PAH and their metabolic activation to the DNA damaging metabolites. These antibodies may prove to be useful in both retrospective and prospective epidemiological studies of various diseases associated with PAH exposure. PMID:3392204

A statistical inference for concentrations of benzo[a]pyrene partially measured in the ambient air of an industrial city in Korea

NASA Astrophysics Data System (ADS)

Kim, Yongku; Seo, Young-Kyo; Baek, Sung-Ok

2013-12-01

Although large quantities of air pollutants are released into the atmosphere, they are partially monitored and routinely assessed for their health implications. This paper proposes a statistical model describing the temporal behavior of hazardous air pollutants (HAPs), which can have negative effects on human health. Benzo[a]pyrene (BaP) is selected for statistical modeling. The proposed model incorporates the linkage between BaP and meteorology and is specifically formulated to identify meteorological effects and allow for seasonal trends. The model is used to estimate and forecast temporal fields of BaP conditional on observed (or forecasted) meteorological conditions, including temperature, precipitation, wind speed, and air quality. The effects of BaP on human health are examined by characterizing health indicators, namely the cancer risk and the hazard quotient. The model provides useful information for the optimal monitoring period and projection of future BaP concentrations for both industrial and residential areas in Korea.

Chemical sensing of Benzo[a]pyrene using Corchorus depressus fluorescent flavonoids.

PubMed

Ahmad, Wajiha; Rana, Nosheen Fatima; Riaz, Sundus; Ahmad, Nasir Mehmood; Hameed, Maryam; Naeem, Ayesha; Tahir, Rabbiya

2018-04-01

Plant phytochemicals, such as flavonoids are in use for the development of optical biosensor. Benzo[a]pyrene (B[a]P), is a pervasive environmental and dietary carcinogen. A fluorescent assay is developed using plant isolated flavonoid for the detection of B[a]P. High content saponins are excluded from the flavonoid-containing methanolic extract of Corchorus depressus by implying reduction of silver ions by saponins resulting in formation of silver nanoparticles. Isolated plant flavonoids are used to develop a spectrofluorometric assay for the detection of B[a]P. Decrease in the flavonoid fluorescence intensity by B[a]P is found to be based on both static and dynamic quenching. Specificity of the assay for B[a]P was tested for other carcinogens belonging to different classes of compounds. Flavonoids-mediated sensing can be implied for the development of new generation of nanoparticle-based biosensors that can be more sensitive and less susceptible to external factors, such as temperature and humidity.

In vitro investigations of α-amylase mediated hydrolysis of cyclodextrins in the presence of ibuprofen, flurbiprofen, or benzo[a]pyrene.

PubMed

Lumholdt, Ludmilla Riisager; Holm, René; Jørgensen, Erling Bonne; Larsen, Kim Lambertsen

2012-11-15

In vitro studies of α-amylase degradation of α-, β- and γ-cyclodextrins and 2-hydroxypropyl-β- and -γ-cyclodextrins were investigated spectrophotometrically by measuring the formation of reducing sugars, the reaction products of α-amylase degradation. This was done to evaluate potential degradation and thereby biological conversion of the cyclodextrins if dosed orally, as the intestinal tract contains α-amylase for digestive purposes. The results demonstrated that only γ- and 2-hydroxypropyl-γ-cyclodextrins can be degraded by α-amylase to a relevant extent, that is, γ- and 2-hydroxypropyl-γ-cyclodextrins have different biopharmaceutical behaviours than the other evaluated cyclodextrins. The rate of degradation was affected by the addition of the inclusion complex forming additives flurbiprofen, ibuprofen and benzo[a]pyrene. This effect between the degradation dynamics and the included additives was caused by a correlation between solubility of the additives and the stability of the complex. Copyright © 2012 Elsevier Ltd. All rights reserved.

Induction of monooxygenation in rainbow trout by polybrominated biphenyls: a comparative study.

PubMed Central

Elcombe, C R; Lech, J J

1978-01-01

Two commercial polychlorinated biphenyl mixtures (Aroclor 1254 and Aroclor 1242) and one polybrominated biphenyl mixture (FireMaster BP-6) were examined for their abilities to induce hepatic microsomal monooxygenation in rainbow trout (Salmo gairdneri). Pretreatment of rainbow trout with Aroclors 1254 and 1242 (150 mg/kg IP) resulted in an approximate 10-fold induction of arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation within 7 days after injection. These enzyme activities remained elevated above control values for at least 2-3 weeks. Administration of FireMaster BP-6 (150 mg/kg IP) also resulted in an induction of several monooxygenase activities. Arylhydrocarbon (benzo[a]pyrene) hydroxylation, ethoxycoumarin-O-deethylation and ethoxyresorufin-O-deethylation were increased by 6-, 3,- and 25-fold, respectively. Only the latter two activities remained elevated two weeks post-injection. Ethylmorphine-N-demethylation was unaffected by the polyhalogenated biphenyls. Significant increases in P-450 hemoprotein were not observed after pretreatment with any of the polyhalogenated biphenyls studied. PMID:209992

Interconnection of Key Microbial Functional Genes for Enhanced Benzo[a]pyrene Biodegradation in Sediments by Microbial Electrochemistry.

PubMed

Yan, Zaisheng; He, Yuhong; Cai, Haiyuan; Van Nostrand, Joy D; He, Zhili; Zhou, Jizhong; Krumholz, Lee R; Jiang, He-Long

2017-08-01

Sediment microbial fuel cells (SMFCs) can stimulate the degradation of polycyclic aromatic hydrocarbons in sediments, but the mechanism of this process is poorly understood at the microbial functional gene level. Here, the use of SMFC resulted in 92% benzo[a]pyrene (BaP) removal over 970 days relative to 54% in the controls. Sediment functions, microbial community structure, and network interactions were dramatically altered by the SMFC employment. Functional gene analysis showed that c-type cytochrome genes for electron transfer, aromatic degradation genes, and extracellular ligninolytic enzymes involved in lignin degradation were significantly enriched in bulk sediments during SMFC operation. Correspondingly, chemical analysis of the system showed that these genetic changes resulted in increases in the levels of easily oxidizable organic carbon and humic acids which may have resulted in increased BaP bioavailability and increased degradation rates. Tracking microbial functional genes and corresponding organic matter responses should aid mechanistic understanding of BaP enhanced biodegradation by microbial electrochemistry and development of sustainable bioremediation strategies.

Comparative Studies on the Toxicokinetics of Benzo[a]pyrene in Pinctada martensii and Perna viridis.

PubMed

Wang, Haihua; Cui, Lili; Cheng, Huamin; Zhang, Yu; Diao, Xiaoping; Wang, Jun

2017-05-01

Research on the kinetics of Benzo[a]pyrene (B[a]P) bioaccumulation in the clam Pinctada martensii and mussel Perna viridis showed that the initial rate of uptake was directly related to the PAH concentrations in the ambient environment. The uptake and depuration rate constants were different at the four B[a]P exposure levels, which indicated that the toxicokinetic rate constants mainly depended on the exposure levels of pollutants to the environment. In addition, the uptake rate constants of B[a]P were higher than the depuration rate constants in the entire experiment. The comparison demonstrated that mussels release B[a]P more rapidly than clams. The bioconcentration factors (BCFs) of B[a]P varied from 3335 to 12892 in the clam and 2373-6235 in the mussel. These findings on the bioaccumulation kinetics for petroleum hydrocarbons, in association with the critical body residue, will be valuable when choosing sensitive organisms to assess the potential ecotoxicological risk to the marine environment.

CHARACTERIZATION AND QUANTITATION OF BENZO[A]PYRENE DNA ADDUCTS BY SOLID-MATRIX LUMINESCENCE. (R824100)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SENSITIVITY ANALYSIS OF THE APPLICATION OF CHEMICAL EXPOSURE CRITERIA FOR COMPARING SITES AND WATERSHEDS

EPA Science Inventory

A methodology was developed for deriving quantitative exposure criteria useful for comparing a site or watershed to a reference condition. The prototype method used indicators of exposures to oil contamination and combustion by-products, naphthalene and benzo(a)pyrene metabolites...

SUSCEPTIBILITY OF PROLIFERATING CELLS TO BENZO(A)PYRENE INDUCED HOMOLOGOUS RECOMBINATION IN MICE. (R825359)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Contamination of agricultural lands by polycyclic aromatic hydrocarbons (Tver region, Russia)

NASA Astrophysics Data System (ADS)

Zhidkin, Andrey; Koshovskii, Timur; Gennadiev, Alexander

2016-04-01

It is important to study sources and concentrations of polycyclic aromatic hydrocarbons (PAHs) in the agriculture soils within areas without intensive contaminations. Our studied object was soil and snow cover in the taiga zone (Tver region, Russia). A total of 52 surface (0-30 cm) and 31 subsurface (30-50 cm) soil samples, and 13 snow samples were collected in 35 soil pits, located in forest, crop and layland soils. Studied concentrations of the following 11 individual compounds: two-ring compounds (diphenyl and naphthalene homologues); three-ring compounds (fluorene, phenanthrene, anthracene); four-ring compounds (chrysene, pyrene, tetraphene); five-ring compounds (perylene, benzo[a]pyrene); and six-ring compounds (benzo[ghi]perylene). Analyses made by specrtofluorometry method at the temperature of liquid nitrogen. The total concentrations of all PAHs in soil samples ranged from 9 to 770 ng*g-1 with a median of 96 ng*g-1. The sum of high molecular weight PAHs was significantly lower than the sum of low molecular weight PAHs in the studied soils. The phenanthrene concentration was highest and ranged from 1.2 to 720 ng*g-1 (medium 72 ng*g-1). Compared PAHs reserves in snow cover (μg*m-2) with the reserves in topsoil layer (μg*m-2 in the upper 30 cm). Low molecular weight PAHs (fluorene, phenanthrene, diphenyl, naphthalene) reserves in snow was less than 20% from the reserves in the soil surface layer. High molecular weight PAHs (benzo[a]pyrene, chrysene, perylene, pyrene and tetraphene) reserves in snow was about 50-70% from the reserves in soil surface layer. High molecular weight PAHs (benzo[ghi]perylene and anthracene) reserves in snow was more than in topsoil. PAHs vertical distribution in soil profiles was statistically examined. The total concentration of all PAHs decreased with depth in all studied forest soils. In the arable soils was no significant trend in domination of PAHs total concentrations in the plowing and subsoil layers. The ratio of topsoil to subsoil concentrations of PAHs is different for differ congeners. Contents of phenanthrene and fluorene predominantly increase with the depth. Content of high molecular weight PAHs (benzo[a]pyrene, anthracene, tetraphene, perylene and pyrene) predominantly decreased with the depth. Other PAHs congeners have indistinct profile distributions in studied pits. Based on studied results PAHs divided to associations with different concentrations, sources and vertical distribution in soils: a) phenanthrene and fluorine; b) naphthalene, diphenyl; c) pyrene, benzo(a)pyrene, tetraphene, perylene, chrysene; d) anthracene and benzo(ghi)perylene. Research is funded by Russian Science Foundation (Project 14-27-00083).

BENZO[A]PYRENE AND ZINC SOLUBILIZATION BY DIGESTIVE FLUIDS OF BENTHIC INVERTEBRATES-A CROSS-PHYLETIC STUDY. (R825353)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

VISUALIZATION OF TISSUE DISTRIBUTION AND METABOLISM OF BENZO[A]PYRENE IN EARLY EMBRYONIC MEDAKA (ORYZIAS LATIPES)

EPA Science Inventory

Fish early life stages are highly sensitive to exposure to persistent bioaccumulative toxicants (PBTs). The factors that contribute to this are unknown, but may include the distribution of PBTs to sensitive tissues during critical stages of development. Multiphoton laser scannin...

EFFECTS OF BENZO[A]PYRENE EXPOSURE ON A FISH POPULATION RESISTANT TO THE TOXIC EFFECTS OF DIOXIN-LIKE COMPOUNDS

EPA Science Inventory

Effects of a model polycyclic aromatic hydrocarbon (PAH) were compared in populations of the estuarine fish Fundulus heteroclitus indigenous to a reference site and one highly contaminated with polychlorinated biphenyls (PCBs) and other compounds. The fish population resident to ...

Comparative Metabolism of Benzo(a)pyrene by Ovarian Microsomes of Various Species

USDA-ARS?s Scientific Manuscript database

Knowledge of the ability of the female reproductive system to metabolize polycyclic aromatic hydrocarbons (PAHs) is critical to the diagnosis and management of female infertility and for risk assessment purposes. The PAHs are a family of widespread pollutants that are released into the environment f...

The Changing Landscape of Chemical Toxicity Values and Challenges Presented with Trichloroethylene

DTIC Science & Technology

2012-12-11

become Risk Management Actions (RMAs) BUILDING STRONG® IRIS Documents Reviewed by DoD Services  Benzo(a)pyrene  Trimethylbenzenes  Dioxin ...4 BUILDING STRONG® Other Chemicals of DoD Interest Undergoing IRIS Reassessment  1,4-Dioxane  Dioxin (cancer)  RDX  Arsenic

OXIDATION OF PERSISTANT ENVIRONMENTAL POLLUTANTS BY A WHITE ROT FUNGUS

EPA Science Inventory

The white rot fungus Phanerochaete chrysosporium degraded DDT [1,1,-bis(4-chlorophenyl)-2,2,2-trichloroethane], 3,4,3',4'-tetrachlorobiphenyl, 2,4,5,2',-4',5'-hexachlorobiphenyl, 2,3,7,8-tetrachlorodibenzo-p-dioxin, lindane (1,2,3,4,5,6-hexachlorocylohexane), and benzo[a]pyrene t...

COST AND BENEFITS OF ALTERED BENZO(A)PYRENE METABOLISM IN A PCB-ADAPTED FISH POPULATION

EPA Science Inventory

We examined populations of an estuarine fish species (Fundulus heteroclitus) resident to a highly contaminated site and a reference site for their ability to metabolize an important environmental pollutant. In previous work, we characterized the fish population resident to this h...

COMPARISON OF THE MORPHOLOGICAL TRANSFORMING ACTIVITIES OF FJORD-REGION PAHS WITH DIBENZO[A,E}PYRENE & BENZO{A}PYRENE

EPA Science Inventory

Po(l'cyclic Aromatic Compound" 1999, Vol. 16. pp. 141-149 ICJ 1999OPA (Overseas Publishers Associationl NV. Reprints available directly from the publisher Published by license under Photocopying permitted by license only the Gordon and Breach Science Publishers imprint.
Print...

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2011 CFR

2011-07-01

... AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Direct Discharge Point Sources That...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Zinc for Rayon Fiber Manufacture that uses the viscose process and Acrylic Fiber Manufacture that uses...

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Direct Discharge Point Sources That...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Zinc for Rayon Fiber Manufacture that uses the viscose process and Acrylic Fiber Manufacture that uses...

77 FR 38523 - Expedited Approval of Alternative Test Procedures for the Analysis of Contaminants Under the Safe...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-28

... of semivolatile organic compounds in finished drinking water. The method analytes are extracted and... semivolatile organic contaminants: Alachlor, atrazine, polychlorinated biphenyls (PCBs), benzo[a]pyrene... approved EPA Method 525.2, Revision 2.0 for each of the 17 regulated semivolatile organic contaminants. EPA...

The roles of diol epoxide and o-quinone pathways in mouse lung tumorigenesis induced by benzo(a)pyrene: relevance to human lung carcinogenesis

EPA Science Inventory

There is sufficient epidemiological evidence supported by experimental data that some PAH-containing complex environmental mixtures pose risks to human health by increasing lung cancer incidence. The International Agency for Research on Cancer has determined that human respirator...

Novel Strategies for the Treatment of Estrogen Receptor-Negative Breast Cancer

DTIC Science & Technology

2007-10-01

quercetin on benzo[a]pyrene induced DNA damage in HepG2 cells as measured by the comet assay” at the Annual Intermountain Meeting of the American Society...Anti-genotoxic effects of Garlic extract and Quercetin as Measured by the Comet Assay, The Journal of the Intermountain Branch of the American

78 FR 51719 - Draft Toxicological Review of Benzo[a]pyrene: In Support of the Summary Information in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... Environmental Assessment (NCEA) within the EPA Office of Research and Development (ORD). EPA is releasing this... Program is a human health assessment program that evaluates quantitative and qualitative risk information... IRIS Program, EPA provides the highest quality science-based human health assessments to support the...

76 FR 510 - National Oil and Hazardous Substances Pollution Contingency Plan; National Priorities List...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... dense non-aqueous phase liquid (DNAPL) containing organic compounds that slowly dissolve into the ground... controls restricting ground water extraction within the northern 62-acre parcel. Soil Contamination As... preliminary remediation goal (PRG) of 8 mg/kg benzo(a)pyrene (BAP) equivalent had not yet been derived...

BENZO(A)PYRENE AND X-RAYS INDUCE REVERSIONS OF THE PINK-EYED UNSTABLE MUTATION IN THE RETINAL PIGMENT EPITHELIUM OF MICE. (R825359)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Antibodies against benzo[a]pyrene in immunized mouse and in lung cancer patients.

PubMed

Ustinov, V A; Matveeva, V A; Kostyanko, M A; Glushkov, A N

2013-09-01

To evaluate the production of antibodies against benzo[a]pyrene (BP) (Ab1) and corresponding antiidiotypic antibodies (Ab2) in mice after immunization with BP-protein conjugate and in lung cancer patients. The Ab1 and Ab2 levels were measured by non-competitive ELISA in blood serum of 10 mice immunized with BP-protein conjugate, and in blood serum of 288 healthy persons and 165 lung cancer patients. The Ab1 level of was 2-fold higher than Ab2 level in blood serum of BP-immunized mice. In lung cancer patients the Ab1 level was almost 3 times higher and the Ab2 level was by 30% higher than these indexes in healthy individuals. The Ab1/Ab2 ratio was 2 in BP-immunized mice and healthy individuals and 1 in lung cancer patients. Our data have shown that the Ab1/Ab2 ratio in lung cancer patients differ from that in healthy individuals and is close to the Ab1/Ab2 ratio in BP-immunized mouse.

Association of aryl hydrocarbon receptor gene polymorphism with the neurobehavioral function and autonomic nervous system function changes induced by benzo[a]pyrene exposure in coke oven workers.

PubMed

Zhang, Hongmei; Nie, Jisheng; Li, Xin; Niu, Qiao

2013-03-01

To analyze the association of aryl hydrocarbon receptor (AhR) gene polymorphism and the neurotoxicity induced by benzo[a]pyrene (B[a]P) in coke oven workers. Subjects, 214 coke oven workers and 81 controls, were detected for neurobehavioral function and autonomic nervous system (ANS) function. Airborne B[a]P concentration, urinary 1-hydroxypyrene level, and AhR gene polymorphisms were determined and analyzed for their association with B[a]P neurotoxicity. Neurobehavioral function and ANS function were significantly decreased and dependent on B[a]P dose. The AhR GG, GA, and AA genotypes in G1661A fitted the Hardy-Weinberg equation, whereas C1549T and G1708A gene mutants were not detected. Indices indicating neurotoxicity showed no significant difference among individuals with AA, GG, or GA genotype except for the confusion-bewilderment (P > 0.05). The AhR gene polymorphism is not thought to correlate with B[a]P neurotoxicity among coke oven workers.

Genome-Wide Functional and Stress Response Profiling Reveals Toxic Mechanism and Genes Required for Tolerance to Benzo[a]pyrene in S. cerevisiae

PubMed Central

O’Connor, Sean Timothy Francis; Lan, Jiaqi; North, Matthew; Loguinov, Alexandre; Zhang, Luoping; Smith, Martyn T.; Gu, April Z.; Vulpe, Chris

2012-01-01

Benzo[a]pyrene (BaP) is a ubiquitous, potent, and complete carcinogen resulting from incomplete organic combustion. BaP can form DNA adducts but other mechanisms may play a role in toxicity. We used a functional toxicology approach in S. cerevisiae to assess the genetic requirements for cellular resistance to BaP. In addition, we examined translational activities of key genes involved in various stress response pathways. We identified multiple genes and processes involved in modulating BaP toxicity in yeast which support DNA damage as a primary mechanism of toxicity, but also identify other potential toxicity pathways. Gene ontology enrichment analysis indicated that DNA damage and repair as well as redox homeostasis and oxidative stress are key processes in cellular response to BaP suggesting a similar mode of action of BaP in yeast and mammals. Interestingly, toxicant export is also implicated as a potential novel modulator of cellular susceptibility. In particular, we identified several transporters with human orthologs (solute carrier family 22) which may play a role in mammalian systems. PMID:23403841

Effect of Soil Aging on the Phytoremediation Potential of Zea mays in Chromium and Benzo[a]Pyrene Contaminated Soils.

PubMed

Chigbo, Chibuike

2015-06-01

This study compared the phytoremediation potential of Zea mays in soil either aged or freshly amended with chromium (Cr) and benzo[a]pyrene (B[a]P). Z. mays showed increased shoot biomass in aged soils than in freshly spiked soils. The shoot biomass in contaminated soils increased by over 50% in aged soil when compared to freshly amended soils, and over 29% more Cr was accumulated in the shoot of Z. mays in aged soil than in freshly amended soil. Planting Z. mays in aged soil helped in the dissipation of more than 31% B[a]P than in freshly spiked soil, but in the absence of plants, there seemed to be no difference between the dissipation rates of B[a]P in freshly and aged co-contaminated soil. Z. mays seemed to enhance the simultaneous removal of Cr and B[a]P in aged soil than in freshly spiked soil and hence can be a good plant choice for phytoremediation of co-contaminated soils.

Assessment of trophic transfer of benzo(a)pyrene genotoxicity from the post-larval pink shrimp F. brasiliensis to the juvenile Florida pompano T. carolinus.

PubMed

Rocha, Arthur José da Silva; Santos, Thaís Cruz Alves; Gomes, Vicente; Bícego, Márcia Caruso; Barbosa, Ana Cecília Rizzatti de Albergaria; Passos, Maria José de Arruda Campos Rocha; Hasue, Fabio Matsu; Van Ngan, Phan

2012-11-01

In the present study, the polycyclic aromatic hydrocarbon (PAH) genotoxicity was investigated in a one-step predator-prey relationship with the trophic-related marine species. Florida pompanos were fed for 5 and 10 days with pink shrimp post larvae previously exposed to benzo(a)pyrene (BaP) concentrations. Parent BaP body burden was measured in samples of Farfantepenaeus brasiliensis. BaP metabolites were determined in bile samples of Trachinotus carolinus and DNA damage was assessed through the comet and erythrocyte nuclear abnormalities (ENAs) assays in fish erythrocytes. BaP body burden increased significantly with the PAH concentration in pink shrimp PLs as well as the fish bile BaP metabolites. Both, comet and ENAs assays indicated significant increase on erythrocyte DNA damage of Florida pompanos fed with BaP-exposed pink shrimp on both feeding periods. The trophic route of BaP genotoxicity is discussed as well as the PAH biotransformation as the inducing mechanism for the DNA damages observed. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of smokeless tobacco and tobacco-related chemical carcinogens on survival of ultraviolet light-inactivated herpes simplex virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dokko, H.; Min, P.S.; Cherrick, H.M.

1991-04-01

Low doses of ultraviolet (UV) light, x-rays, photodynamic treatment, or aflatoxins increase the survival of UV-irradiated virus in cells. This effect is postulated to occur by enhancement of the error-prone cellular repair function, which could also be associated with oncogenic cell transformation. The present study was designed to investigate whether treatment of green monkey kidney cells with water extract of snuff (snuff extract), benzo(a)pyrene, nicotine, or tobacco-specific N'-nitrosamines would result in enhanced survival of UV-irradiated herpes simplex virus (HSV). Exposure of the cells with snuff extract, benzo(a)pyrene, N'-nitrosonornicotine, or 4-(N-methyl-N'-nitrosamino)-1-(3-pyridyl)-1-butanone resulted in an enhancement of survival of UV-irradiated HSV typemore » 1 compared with the control whereas exposure of the cells with nicotine did not. These data indicate that the water-extractable component of snuff and tobacco-related chemical carcinogens increase the cellular repair mechanism and provides for increased survival of UV-irradiated HSV.« less

Nitration of benzo[a]pyrene adsorbed on coal fly ash particles by nitrogen dioxide: role of thermal activation.

PubMed

Kristovich, Robert L; Dutta, Prabir K

2005-09-15

Nitration of benzo[a]pyrene (BaP) by nitrogen dioxide (NO2) adsorbed on the surface of thermally activated coal fly ash and model aluminosilicate particles led to the formation of nitrobenzo[a]pyrenes as verified by extraction and gas chromatography/mass spectrometry (GC/MS). In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) was utilized to follow the nitration reaction on the surface of zeolite Y. Nitrobenzo[a]pyrene formation was observed along with the formation of nitrous acid and nitrate species. The formation of the BaP radical cation was also observed on thermally activated aluminosilicate particles by electron spin resonance (ESR) spectroscopy. On the basis of GC/MS, DRIFTS, and ESR spectroscopy results, a mechanism of nitration involving intermediate BaP radical cations generated on thermally activated aluminosilicate particles is proposed. These observations have led to the hypothesis that nitration of adsorbed polyaromatic hydrocarbons on coal fly ash by reaction with nitrogen oxides can occur in the smokestack, but with the aging of the fly ash particles, the extent of the nitration reaction will be diminished.

Study of polycyclic aromatic hydrocarbons in atmospheric particulate matter of an urban area with iron and steel mills.

PubMed

Menezes, Helvécio C; Cardeal, Zenilda L

2012-07-01

Polycyclic aromatic hydrocarbons (PAHs) were analyzed from ambient air particulate matter <10 µm (PM(10) ) and the total suspended particulate (TSP) phase continuously for a period of six months (May-October 2010) at five sampling sites located in the urban area of Divinópolis (Minas Gerais), southeastern Brazil, near iron and steel mills. The carcinogenic potency of priority PAHs relative to benzo[a]pyrene was estimated for a period of six months. Benzo[a]pyrene equivalents were 7.52 ng/m(3) for the study period. The estimated risk of lifetime lung cancer was 6.5 × 10(-4) . A model based on the diagnostic ratio and principal component analysis was applied for source apportionment. Considering the entire study period, the burning of biomass and fuel oil accounted for about 70% of the PAH profile. An inventory was performed during the monitoring period, with 37 companies representing major industries located in the urban area. The observations were consistent with the distribution of sources and indicated that the iron and steel sector was the largest contributor. Copyright © 2012 SETAC.

Benzo[a]pyrene and Benzo[k]fluoranthene in Some Processed Fish and Fish Products

PubMed Central

Olatunji, Olatunde S.; Fatoki, Olalekan S.; Opeolu, Beatrice O.; Ximba, Bhekumusa J.

2015-01-01

In this study, the concentration levels of the probable carcinogenic PAH fractions, benzo[a]pyrene (BaP) and benzo[k]fluoranthrene (BkF) in fillets of some processed fish species were investigated. Fish species comprising Merluccius poli (hake), Tyrsites atun (snoek), Seriola lalandi (yellow-tail) and Brama brama (angel fish) were bought in fish shops at Gordon’s Bay, Western Cape, South Africa. The fish were gutted, filleted and prepared for edibility by frying, grilling and boiling. Polycyclic aromatic hydrocarbons were extracted from each homogenized fish sample, cleaned-up using solid phase extraction (SPE), and analysed for the PAH fractions, BaP and BkF using a Gas Chromatograph coupled with a Flame Ionization Detector (GC-FID). The sum of the two PAHs (∑2PAH) i.e., BaP and BkF ranged between 0.56 and 1.46 µg/kg, in all boiled, grilled and fried fish species. The fried fish extracts showed significantly higher (p < 0.05) abundance of ∑2PAH, than grilled and boiled fish. Dietary safety and PAHs toxicity was also discussed. PMID:25607603

Detection of benzo[a]pyrene-guanine adducts in single-stranded DNA using the α-hemolysin nanopore

NASA Astrophysics Data System (ADS)

Perera, Rukshan T.; Fleming, Aaron M.; Johnson, Robert P.; Burrows, Cynthia J.; White, Henry S.

2015-02-01

The carcinogenic precursor benzo[a]pyrene (BP), a polycyclic aromatic hydrocarbon, is released into the environment through the incomplete combustion of hydrocarbons. Metabolism of BP in the human body yields a potent alkylating agent (benzo[a]pyrene diol epoxide, BPDE) that reacts with guanine (G) in DNA to form an adduct implicated in cancer initiation. We report that the α-hemolysin (αHL) nanopore platform can be used to detect a BPDE adduct to G in synthetic oligodeoxynucleotides. Translocation of a 41-mer poly-2‧-deoxycytidine strand with a centrally located BPDE adduct to G through αHL in 1 M KCl produces a unique multi-level current signature allowing the adduct to be detected. This readily distinguishable current modulation was observed when the BPDE-adducted DNA strand translocated from either the 5‧ or 3‧ directions. This study suggests that BPDE adducts and other large aromatic biomarkers can be detected with αHL, presenting opportunities for the monitoring, quantification, and sequencing of mutagenic compounds from cellular DNA samples.

Benzo[a]pyrene-7,8-dihydrodiol promotes checkpoint activation and G2/M arrest in human bronchoalveolar carcinoma H358 cells.

PubMed

Caino, M Cecilia; Oliva, Jose L; Jiang, Hao; Penning, Trevor M; Kazanietz, Marcelo G

2007-03-01

Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens that require metabolic activation inside cells. The proximate carcinogens PAH-diols can be converted to o-quinones by aldo-keto reductases (AKRs) or to diol-epoxides by cytochrome P450 (P450) enzymes. We assessed the effect of benzo[a]pyrene-7,8-dihydrodiol (BPD) on proliferation in p53-null bronchoalveolar carcinoma H358 cells. BPD treatment led to a significant inhibition of proliferation and arrest in G2/M in H358 cells. The relative contribution of the AKR and P450 pathways to cell cycle arrest was assessed. Overexpression of AKR1A1 did not affect cell proliferation or cell cycle progression, and benzo[a]pyrene-7,8-dione did not cause any noticeable effect on cell growth, suggesting that AKR1A1 metabolic products were not involved in the antiproliferative effect of BPD. On the other hand, blockade of P450 induction or inhibition of P450 activity greatly impaired the effect of BPD. Moreover, P450 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin significantly enhanced the antiproliferative effect of BPD. Mechanistic studies revealed that BPD caused a DNA damage response, Chk1 activation, and accumulation of phospho-Cdc2 (Tyr15) in H358 cells, effects that were impaired by an ataxia-telangectasia mutated (ATM)/ATM-related (ATR) inhibitor. Similar results were observed in human bronchoepithelial BEAS-2B cells, arguing for analogous mechanisms in tumorigenic and immortalized nontumorigenic cells lacking functional p53. Our data suggest that a p53-independent pathway operates in lung epithelial cells in response to BPD that involves P450 induction and subsequent activation of the ATR/ATM/Chk1 damage check-point pathway and cell cycle arrest in G2/M.

Benzo[a]pyrene in urban environments of eastern Moscow: pollution levels and critical loads

NASA Astrophysics Data System (ADS)

Kasimov, Nikolay S.; Kosheleva, Natalia E.; Nikiforova, Elena M.; Vlasov, Dmitry V.

2017-02-01

Polycyclic aromatic hydrocarbons (PAHs), particularly benzo[a]pyrene (BaP), are toxic compounds emitted from various anthropogenic sources. Understanding the BaP concentrations, dynamics and decomposition in soil is required to assess the critical loads of BaP in urban environments. This study is the first attempt to evaluate all major input and output components of benzo[a]pyrene (BaP) balance and to calculate the permissible load on the urban environment in different land-use zones in the Eastern district of Moscow. BaP contamination of the snow cover in the Eastern district of Moscow was related to daily BaP fallout from the atmosphere. In 2010, the mean content of the pollutant in the snow dust was 1942 ng g-1, whereas the average intensity of its fallout was 7.13 ng m-2 per day. Across the territory, BaP winter fallout intensities varied from 0.3 to 1100 ng m-2 per day. The average BaP content in the surface (0-10 cm) soil horizons was 409 ng g-1, which is 83 times higher than the local background value and 20 times higher than the maximum permissible concentration (MPC) accepted in Russia. The variations in soil and snow BaP concentrations among different land-use zones were examined. A significant contribution of BaP from the atmosphere to urban soils was identified. Based on the measurements of BaP atmospheric fallout and BaP reserves in the soils, the critical loads of BaP for the land-use zones in the Eastern district were calculated for different values of degradation intensity and different exposure times. It was established that at an annual degradation intensity of 1-10 %, ecologically safe BaP levels in the soils of all land-use zones, excluding the agricultural zone, will only be reached after many decades or centuries.

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase Imore » metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 µM), and higher intrinsic clearance at lower substrate concentrations (<0.07 µM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.« less

Low-dose benzo(a)pyrene and its epoxide metabolite inhibit myogenic differentiation in human skeletal muscle-derived progenitor cells.

PubMed

Chiu, Chen-Yuan; Yen, Yuan-Peng; Tsai, Keh-Sung; Yang, Rong-Sen; Liu, Shing-Hwa

2014-04-01

The risk of low birth weights is elevated in prenatal exposure to polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous environmental pollutants generated from combustion of organic compounds, including cigarette smoke. We hypothesized that benzo(a)pyrene (BaP), a member of PAHs existing in cigarette smoke, may affect the myogenesis to cause low birth weights. We investigated the effects of BaP and its main metabolite, benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), on the myogenic differentiation of human skeletal muscle-derived progenitor cells (HSMPCs). HSMPCs were isolated by a modified preplate technique and cultured in myogenic differentiation media with or without BaP and BPDE (0.25 and 0.5 μM) for 4 days. The multinucleated myotube formation was morphologically analyzed by hematoxylin and eosin staining. The expressions of myogenic differentiation markers and related signaling proteins were determined by Western blotting. Both BaP and BPDE at the submicromolar concentrations (0.25 and 0.5 μM) dose-dependently repressed HSMPCs myogenic differentiation without obvious cell toxicity. Both BaP and BPDE inhibited the muscle-specific protein expressions (myogenin and myosin heavy chain) and phosphorylation of Akt (a known modulator in myogenesis), which could be significantly reversed by the inhibitors for aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and nuclear factor (NF)-κB. BaP- and BPDE-activated NF-κB-p65 protein phosphorylation could also be attenuated by both AhR and ER inhibitors. The inhibitory effects of BaP and BPDE on myogenesis were reversed after withdrawing BaP exposure, but not after BPDE withdrawal. These results suggest that both BaP and BPDE are capable of inhibiting myogenesis via an AhR- or/and ER-regulated NF-κB/Akt signaling pathway.

ACTIVATION OF DIOXIN RESPONSE ELEMENT (DRE)-ASSOCIATED GENES BY BENZO(A)PYRENE 3,6-QUINONE AND BENZO(A)PYRENE 1,6-QUINONE IN MCF-10A HUMAN MAMMARY EPITHELIAL CELLS

PubMed Central

Burchiel, Scott W.; Thompson, Todd A.; Lauer, Fredine T.; Oprea, Tudor I.

2007-01-01

Benzo(a)pyrene (BaP) is a known human carcinogen and a suspected breast cancer complete carcinogen. BaP is metabolized by several metabolic pathways, some having bioactivation and others detoxification properties. BaP-quinones (BPQs) are formed via cytochrome P450 and peroxidase dependent pathways. Previous studies by our laboratory have shown that BPQs have significant growth promoting and anti-apoptotic activities in human MCF-10A mammary epithelial cells examined in vitro. Previous results suggest that BPQs act via redox-cycling and oxidative stress. However, because two specific BPQs (1,6-BPQ and 3,6-BPQ) differed in their ability to produce reactive oxygen species (ROS) and yet both had strong proliferative and EGF receptor activating activity, we utilized mRNA expression arrays and qRT-PCR to determine potential pathways and mechanisms of gene activation. The results of the present studies demonstrated that 1,6-BPQ and 3,6-BPQ activate dioxin response elements (DRE, also known as xenobiotic response elements, XRE) and anti-oxidant response elements (ARE, also known and electrophile response elements, EpRE). 3,6-BPQ had greater DRE activity than 1,6-BPQ, whereas the opposite was true for the activation of ARE. Both 3,6-BPQ and 1,6-BPQ induced oxidative stress associated genes (HMOX1, GCLC, GCLM, and SLC7A11), phase 2 enzyme genes (NQO1, NQO2, ALDH3A1) PAH metabolizing genes (CYP1B1, EPHX1, AKR1C1), and certain EGF receptor associated genes (EGFR, IER3, ING1, SQSTM1 and TRIM16). The results of these studies demonstrate that BPQs activate numerous pathways in human mammary epithelial cells associated with increased cell growth and survival that may play important roles in tumor promotion. PMID:17466351

40 CFR 414.101 - Toxic pollutant effluent limitations and standards for direct discharge point sources that do not...

Code of Federal Regulations, 2011 CFR

2011-07-01

... GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Direct Discharge Point Sources...(k)fluoranthene 47 19 Benzo(a)pyrene 48 20 Bis(2-ethylhexyl) phthalate 258 95 Carbon Tetrachloride... micrograms per liter. 2 Total Zinc for Rayon Fiber Manufacture that uses the viscose process and Acrylic...

40 CFR 414.101 - Toxic pollutant effluent limitations and standards for direct discharge point sources that do not...

Code of Federal Regulations, 2010 CFR

2010-07-01

... GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Direct Discharge Point Sources...(k)fluoranthene 47 19 Benzo(a)pyrene 48 20 Bis(2-ethylhexyl) phthalate 258 95 Carbon Tetrachloride... micrograms per liter. 2 Total Zinc for Rayon Fiber Manufacture that uses the viscose process and Acrylic...

MORPHOLOGICAL TRANSFORMATION OF C3H10T1/2CL8 CELLS BY CYCLOPENTA-FUSED DERIVATIVES OF BENZO[A]PYRENE AND BENZO[E]PYRENE

EPA Science Inventory

Cyclopenta-fused homologs of polycyclic aromatic hydrocarbons (PAH) have proven to be more genotoxic and tumorigenic than their parent PAHs. In an effort to uncover their mechanisms of metabolic activation, the morphological transforming activities of dibenzo[k,mno]acephenanthryl...

Application of the Margin of Exposure (MoE) Approach to Substances in Food that are Genotoxic and Carcinogenic Example: Benzo[a]pyrene and polycyclic aromatic hydrocarbons

EPA Science Inventory

This paper presents the work of an expert group established by the International Life Sciences Institute - European branch (ILSI Europe) to follow up the recommendations of an international conference on "Risk Assessment of Compounds that are both Genotoxic and Carcinogenic: New ...

Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of CYP1 enzymes

USDA-ARS?s Scientific Manuscript database

Smoking is a major risk factor for osteoporosis and fracture. Here, we show that smoke toxins and environmental chemicals such as benzo[a]pyrene (BaP), 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD), and 3-methyl cholanthrene, which are well known aryl hydrocarbon receptor (AHR) agonists, induce osteocla...

Polynuclear aromatic hydrocarbons in forest fire smoke

Treesearch

Charles K. McMahon; Skevos N. Tsoukalas

1978-01-01

The occurrence of polynuclear aromatic hydrocarbons (PAH) in the combustion products of carbonaceous fuels is a well known phenomenon. Several PAW are known to be carcinogenic in animals. Benzo[a]pyrene (BaP) is the most well-known and studied compound of those classified by the National Academy of Science (NAS) as strongly carcinogenic. Ambient BaP concentrations...

Oxidation of anthracene and benzo[a]pyrene by laccases from Trametes versicolor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Collins, P.J.; Dobson, A.D.W.; Kotterman, M.J.J.

1996-12-01

Polycyclic aromatic hydrocarbons, particularly benzene homologs, are highly toxic organic pollutants. One of the three major groups of extracellular oxidative enzymes involved in the white rot fungal lignin degradative process are laccases. This study presents evidence indicating that laccase has a role in PAH oxidation by white rot fungi. 36 refs., 5 figs., 1 tab.

INDUCTION OF CYP1A1 AND CYP1B1 IN T-47D HUMAN BREAST CANCER CELLS BY BENZO[A]PYRENE IS DIMINISHED BY ARSENITE. (R827180)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

PROPOSED PROCEDURE FOR DERIVATION OF REGULATORY VALUES FOR CARCINOGENIC AIRBORNE POLYCYCLIC AROMATIC HYDROCARBONS (PAHS) BASED ON COAL TAR PITCH (CTP) VOLATILES

EPA Science Inventory

A procedure for estimating upper bound lifetime human cancer risk from air levels of 6 common carcinogenic PAHs, termed "PAHs of concern", is proposed. These PAHs are benzo(a)pyrene, benz(a)anathracene, benzo(k)flouranthene, indeno(1,2,3-c,d)pyrene and chrysene. In application,...

40 CFR Appendix Ix to Part 261 - Wastes Excluded Under §§ 260.20 and 260.22

Code of Federal Regulations, 2011 CFR

2011-07-01

... delisting level established in Condition (1), or is at a level in the ground water or soil higher than the... violation of the delisting petition and a possible revocation of the decision. Ampex Recording Media... using distilled water. (B) Organics: Benzene, 0.87 ppm; Benzo(a)anthracene, 0.10 ppm; Benzo(a)pyrene, 0...

BENZO[A]PYRENE AND BENZO[C]PHENANTHRENE: THE EFFECT OF STRUCTURE ON THE BINDING OF WATER MOLECULES TO THE DIOL EPOXIDES

EPA Science Inventory

ABSTRACT
The interaction with water of the diol epoxides (DEs) of both a planar and a non-planar PAH have been examined using molecular dynamics. To determine probable water locations around the DE for later use in the study of DE protonation, molecular dynamics simulations u...

CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

EPA Science Inventory

Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

METABOLISM OF BENZO[A]PYRENE AND PERSISTENCE OF DNA ADDUCTS IN THE BROWN BULLHEAD (ICTALURUS NEBULOSUS)

EPA Science Inventory

The in vitro metabolism of [3H]benzo[a]pyrene (BP) and [14C]benzo[a]pyrene-7,8-dihydrodiol (BP-7,8-diol) by liver of brown bullhead (Ictalurus Nebulosus) was characterized, as was the formation and persistence of BP-DNA adducts in vivo. ompared to rat liver microsomes, bullhead l...

Polycyclic aromatic hydrocarbons in frying oils and snacks.

PubMed

Purcaro, Giorgia; Navas, José A; Guardiola, Francesc; Conte, Lanfranco S; Moret, Sabrina

2006-01-01

The high incidence of lung cancer observed among Chinese women has been associated with exposure to fumes from cooking oil. Polycyclic aromatic hydrocarbons (PAHs) are a class of potentially mutagenic substances emitted from cooking oils heated at high temperatures. The objective of this study was to investigate whether deep frying with different oils under different conditions leads to the development of PAHs either in the oil or in the fried product (snacks). PAH analysis was carried out with solid-phase extraction followed by reverse-phase high-performance liquid chromatography and spectrofluorometric detection. Different oils were used to fry chips and extruded snacks in different industrial plants (continuous frying) at temperatures between 170 and 205 degrees C, and peanut oil was used to fry French fries and fish (discontinuous frying) at temperatures between 160 and 185 degrees C. No appreciable differences in PAH load was observed in the same oil before and after frying. Both before and after frying, the benzo[a]pyrene concentration in oils ranged from trace to 0.7 ppb. All the analyzed samples, including oils from fried snacks, had benzo[a]pyrene concentrations well below the 2 ppb limit recently proposed by the European Community.

A common carcinogen benzo[a]pyrene causes p53 overexpression in mouse cervix via DNA damage.

PubMed

Gao, Meili; Li, Yongfei; Sun, Ying; Long, Jiangang; Kong, Yu; Yang, Shuiyun; Wang, Yili

2011-09-18

Benzo[a]pyrene (BaP) is cytotoxic and/or genotoxic to lung, stomach and skin tissue in the body. However, the effect of BaP on cervical tissue remains unclear. The present study detected DNA damage and the expression of the p53 gene in BaP-induced cervical tissue in female mice. Animals were intraperitoneally injected and orally gavaged with BaP at the doses of 2.5, 5, and 10mg/kg twice a week for 14 weeks. The single-cell gel electrophoresis (SCGE) assay was used to detect the DNA damage. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to detect the expression of p53 protein and p53 mRNA, respectively. The results showed that BaP induced a significant and dose-dependent increase of the number of cells with DNA damaged and the tail length as well as Comet tail moment in cervical tissue. The expression level of p53 protein and mRNA was increased. The results demonstrate that BaP may show toxic effect on the cervix by increasing DNA damage and the expression of the p53 gene. Copyright © 2011 Elsevier B.V. All rights reserved.

Modulation of neurotoxic behavior in F-344 rats by temporal disposition of benzo(a)pyrene.

PubMed

Saunders, Crystal R; Ramesh, Aramandla; Shockley, Dolores C

2002-03-24

The behavioral changes caused by benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, were monitored, and also its metabolite levels in cerebellum and cortex were measured in BaP treated rats to see if any relationship existed between these two aspects. Rats were administered 0, 25, 50, 100, and 200 mg/kg of BaP in peanut oil by oral gavage. Plasma, and brain tissue (cerebellum and cortex) samples were collected at 0, 2, 4, 6, 12, 24, 48, 72 and 96 h post administration. Neurotoxic effects peaked at 2 h after dosing and lasted 48 h after dosing for all dose groups. The metabolite levels remained the same from 2 to 4 h, reached a peak at 6 h post gavage and showed a gradual decline returning to baseline levels at 72 h when the motor activity of treatment groups also returned to control levels, indicating recovery from the effects of BaP. A significant (P<0.05) correlation between neurotoxic effects and BaP plasma, and brain metabolite concentrations suggests that metabolism plays an important role in modulating the neurobehavioral effects of BaP.

EU marker polycyclic aromatic hydrocarbons in food supplements: analytical approach and occurrence

PubMed Central

Zelinkova, Zuzana; Wenzl, Thomas

2015-01-01

Several food supplements comprising botanical, oil and bee products collected from retail markets in different countries were tested for the occurrence of 4 EU marker Polycyclic aromatic hydrocarbons (PAHs; benz[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene). A robust GC/MS-based stable-isotope dilution method was used taking into account the differences in the type of matrices. The accuracy of the results was assessed by implementing several quality control tools. Sixty-eight samples of 94 analysed products exceeded the level of 0.5 μg/kg for the sum of the four EU marker PAHs (ΣPAH4). Benzo[a]pyrene exceeded the limit of quantification in 49 samples. The PAH with the highest abundance in all products was chrysene. On average, propolis extracts and other bee products showed relatively high levels of ΣPAH4 (mean 188.2 μg/kg), whereas the contamination levels of fish oil supplements were very low or mostly undetectable. Considerably high ΣPAH4 amounts found in some samples could remarkably increase the daily exposure of consumers to PAHs, demonstrating the need for continuous monitoring of ΣPAH4 in food supplements. PMID:26467752

A new lactoferrin- and iron-dependent lysosomal death pathway is induced by benzo[a]pyrene in hepatic epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gorria, Morgane; Tekpli, Xavier; Rissel, Mary

2008-04-15

While lysosomal disruption seems to be a late step of necrosis, a moderate lysosomal destabilization has been suggested to participate early in the apoptotic cascade. The origin of lysosomal dysfunction and its precise role in apoptosis or apoptosis-like process still needs to be clarified, especially upon carcinogen exposure. In this study, we focused on the implication of lysosomes in cell death induced by the prototype carcinogen benzo[a]pyrene (B[a]P; 50 nM) in rat hepatic epithelial F258 cells. We first demonstrated that B[a]P affected lysosomal morphology (increase in size) and pH (alkalinization), and that these changes were involved in caspase-3 activation andmore » cell death. Subsequently, we showed that lysosomal modifications were partly dependent on mitochondrial dysfunction, and that lysosomes together with mitochondria participate in B[a]P-induced oxidative stress. Using two iron chelators (desferrioxamine and deferiprone) and siRNA targeting the lysosomal iron-binding protease lactoferrin, we further demonstrated that both lysosomal iron content and lactoferrin were required for caspase-3 activation and apoptosis-like cell death.« less

Polycyclic aromatic hydrocarbons in commercial fish and lobsters from the coastal waters of Madagascar following an oil spill in August 2009.

PubMed

Rumney, Heather S; Laruelle, Franck; Potter, Kerry; Mellor, Philip K; Law, Robin J

2011-12-01

Concentrations of polycyclic aromatic hydrocarbons were determined in species of commercial fish and lobsters following an oil-spill just off the protected Madagascan coastline. Samples were collected along the coastline within and outside the affected area. Summed PAH concentrations ranged from 1.9 μg kg(-1) to 63 μg kg(-1) wet weight, but with no higher molecular weight PAHs (>202 Da) being detected. All concentrations of benzo[a]pyrene, benz[a]anthracene and dibenz[a,h]anthracene were <0.1 μg kg(-1) wet weight, well within the EU and UK set limits for the protection of human health. Additionally, samples were calculated as the benzo[a]pyrene toxic equivalency quotient (TEQ) and found to be well below the level of concern in relation to health of human consumers. Evaluation of the biota PAH data indicated the origin of PAH was predominantly petrogenic with >80% arising from oil sources. Profile studies indicate a low-level multisource petrogenic contamination probably representing a pre-spill background for the area. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Cell metabolic changes of porphyrins and superoxide anions by anthracene and benzo(a)pyrene.

PubMed

Uribe-Hernández, Raúl; Pérez-Zapata, Aura J; Vega-Barrita, María L; Ramón-Gallegos, Eva; Amezcua-Allieri, Myriam A

2008-09-01

The aim of this work was to evaluate the induction of protoporphyrins IX (PpIX) activity and superoxide anions (SO) in human leukocytes exposed to anthracene (ANT) and benzo(a)pyrene (B(a)P). The leukocyte LC(50)s for both hydrocarbons and the PpIX accumulation and SO overproduction were measured. The LC(50)s were 0.35 and 3.23μM for ANT and B(a)P, respectively. A linear relationship (r=0.97, p<0.01) between PpIX and ANT concentration was obtained. The induced accumulation of PpIX was proportional (r=0.63, p<0.01) to B(a)P concentration. SO overproduction showed a linear relationship (r=0.83, p<0.05) with ANT concentrations. The linear regression analysis of the effect of B(a)P on the superoxide anion overproduction showed a good coefficient (r=0.97, p<0.01), showed that ANT and B(a)P exposure induces PpIX accumulation, probably by disruption of the haem biosynthesis. ANT and B(a)P induce SO overproduction, perhaps through a process of redox cycling. Copyright © 2008 Elsevier B.V. All rights reserved.

Newsagents' daily personal exposures to benzo(a)pyrene in Genoa, Italy

NASA Astrophysics Data System (ADS)

Piccardo, Maria Teresa; Stella, Anna; Redaelli, Anna; Minoia, Claudio; Valerio, Federico

Daily personal exposures to benzo(a)pyrene (BaP) of 31 newsagents working in Genoa, Italy, were evaluated throughout 1998 during two different seasonal periods (February-April and May-June). Exposures of smoker and non-smoker subjects were compared. The highest BaP exposures were those of smokers during the cold period (2.20±0.84 ng/m 3). During this same period, the BaP exposure for non-smoker subjects was 1.00±0.32 ng/m 3. Both smoker and non-smoker exposures showed a seasonal dependence, with the lowest values occurring in the warm period (smokers: 1.46±0.72 ng/m 3, non-smokers: 0.65±0.25 ng/m 3). Compared to the cold period, the warm period produced a nearly 35% reduction in BaP exposures in both smoker and non-smoker subjects. A linear correlation was observed between personal exposures and number of cigarettes smoked daily. An increase in average daily BaP exposure of 0.071±0.009 ng/m 3 for every cigarette, due to passive smoke, was calculated. Mean BaP concentrations calculated from fixed monitoring stations were nearly 40% higher than mean personal exposures of non-smoker newsagents.

Effect of benzo[a]pyrene on the production of vascular endothelial growth factor by human eosinophilic leukemia EoL-1 cells.

PubMed

Gu, Jie; Chan, Lai-Sheung; Wong, Chris Kong-Chu; Wong, Ngok-Shun; Wong, Chun-Kwok; Leung, Kok-Nam; Mak, Naiki K

2011-01-01

Benzo[a]pyrene (BaP) has been shown to affect both the development and response of T and B cells in the immune system. However, the effect of BaP on other immune cells, such as eosionophils, is unknown. In this study, we investigated the effect of BaP on the production of vascular endothelial growth factor (VEGF) using an in vitro eosinophilic EoL-1 cell and human umbilical vein endothelial cell (HUVEC) co-culture system. EoL-1-conditioned medium was found to promote the growth of HUVEC in a time-dependent manner. The growth stimulating activity was due to the production of VEGF by the EoL-1 cells. The production of VEGF was correlated with the enhanced expression of the phosphorylated form of extracellular signal-regulated kinases (p-ERKs) and the upregulated expression of VEGF mRNA. Furthermore, BaP-induced expression of VEGF mRNA was reduced by the ERK inhibitor PD98059. Results from this study suggested that BaP might affect the growth of endothelial cells through the modulation of VEGF production by eosinophils.

Effect of petroleum-related pollutants on Aurelia growth and development. Progress report, September 12, 1977--November 15, 1978

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spangenberg, D.B.

Strobilation initiation studies revealed that phenol and aniline inhibited strobilation initiation and phenol (at lower dosages) caused a reversal of strobilation initiation whereas benzo(a)pyrene did not affect this process. Ephyra abnormalities were created by phenol (abnormal pulsing and a cup-shaped morphology) naphthalene (abnormal lappet formation) and aniline (impaired nematocyst synthesis). Statolith synthesis was reduced by aniline, naphthalene, phenol, and benzo(a)pyrene. Budding rates were likewise retarded by phenol and aniline as was the metamorphosis of planulae into polyps. Tentacle regeneration of mature polyps was not affected by phenol or aniline. A specific testing procedure for the administration of the water insolublemore » hydrocarbons was developed using sonication. The hydrocarbons were reduced to very fine particles with sonication and the minute particles were taken into the jellyfish. New jellyfish cultures were developed from medusae collected in Norfolk. These organisms responded to iodide, thyroxine, and hydrocarbons in a similar manner as the Texas Aurelia. The hydrocarbon effects on strobilation initiation and ephyra formation suggested that the hydrocarbons affected thyroxine synthesis and/or action in the jellyfish (and other organisms) and call for detailed studies as to their specific mechanisms of action.« less

UVA radiation induced ultrafast electron transfer from a food carcinogen benzo[a]pyrene to organic molecules, biological macromolecules, and inorganic nano structures.

PubMed

Banerjee, Soma; Sarkar, Soumik; Lakshman, Karthik; Dutta, Joydeep; Pal, Samir Kumar

2013-04-11

Reactions involving electron transfer (ET) and reactive oxygen species (ROS) play a pivotal role in carcinogenesis and cancer biochemistry. Our present study emphasizes UVA radiation induced ET reaction as one of the key aspects of a potential carcinogen, benzo[a]pyrene (BP), in the presence of a wide variety of molecules covering organic p-benzoquinone (BQ), biological macromolecules like calf-thymus DNA (CT-DNA), human serum albumin (HSA) protein, and inorganic zinc oxide (ZnO) nanorods (NRs). Steady-state and picosecond-resolved fluorescence spectroscopy have been used to monitor such ET reactions. Physical consequences of BP association with CT-DNA have been investigated through temperature-dependent circular dichroism (CD) spectroscopy. The temperature-dependent steady-state, picosecond-resolved fluorescence lifetime and anisotropy studies reveal the effect of temperature on the perturbation of such ET reactions from BP to biological macromolecules, highlighting their temperature-dependent association. Furthermore, the electron-donating property of BP has been corroborated by measuring wavelength-dependent photocurrent in a BP-anchored ZnO NR-based photodevice, offering new physical insights for the carcinogenic study of BP.

Public health assessment for Allied Chemical and Ironton Coke, Ironton, Lawrence County, Ohio, Region 5. Cerclis No. OHD043730217. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-05-16

The Allied Chemical/Ironton Coke site is in the City of Ironton, Lawrence County Ohio. The areas of concern for this public health assessment are the former Coke Plant and Lagoon Area and the Tar Plant. From 1920 to the 1960's, waste was discharged into the lagoon area. Soil samples showed the on-site surface soil to be contaminated with cyanide, phenolics, benzene, naphthalene, and benzo(a)pyrene (a polynuclear aromatic hydrocarbon). Groundwater analysis detected a number of volatile and semi-volatile organic compounds plus cyanide. Sediment samples from Ice Creek, a stream bordering the lagoon area contained low levels of cyanide, phenolics, and naphthalene.more » The site poses a public health hazard because of the potential for long-term exposure to cyanide, benzo(a)pyrene, and naphthalene in on-site soils. The Allied Chemical Coke site also poses an indeterminate public health hazard because of the potential impact on a public water supply. The residents who obtain their drinking water from the Coal Grove well field are potentially at risk of exposure to chemicals originating from the site.« less

EFFECTS OF BENZO[A]PYRENE AND ARSENITE ON CYP1A1 AND CYP1B1 MRNA LEVELS IN T-47D HUMAN BREAST CANCER CELLS: DETERMINATION BY A BRANCHED DNA ASSAY. (R827180)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walton, B.T.

In the present study, acute and chronic toxicities of five PAHs (naphthalene, anthracene, benz(a)anthracene, pyrene, and benzo(a)pyrene) and an oxygenated PAH derivative (anthrone) were determined in a terrestrial insect, Acheta domesticus (L.), with emphasis on the influence of route of entry on toxicity. Hexamethylphosphoric triamide (hempa) was included in the chronic tests since this chemosterilant is a useful reference compound for investigations of reproductive effects of chemicals in insects.

EXPLORING RELATIONSHIPS BETWEEN OUTDOOR AIR PARTICULATE-ASSOCIATED POLYCYCLIC AROMATIC HYDROCARBON AND PM2.5: A CASE STUDY OF BENZO(A)PYRENE IN CALIFORNIA METROPOLITAN REGIONS

EPA Science Inventory

Polycyclic aromatic hydrocarbons (PAHs) and particulate matter (PM) are co-pollutants emitted as by-products of combustion processes. Convincing evidence exists for PAHs as a primary toxic component of fine PM (PM_2.5). Because PM_2.5 is listed by the US EPA a...

Environmental Assessment for Restoration and Stabilization of Eastern Shoreline MacDill AFB, Florida

DTIC Science & Technology

2005-12-01

heal stress , and machinery injuries. Construction would not involve any unique hazards and all construction methods would comply with Occupational...slips, heat stress , and machinery injuries. Construction would not involve any unique hazards, and all construction methods would comply with OSHA...Chloropropane, Benzene, Cumine , Naphthalene, benzo(b)flouranthene, toluene Soils: Benzo(a)pyrene, dibenzo(a,h)anthracene, Pb, naphthalene, toluene Surface

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2012 CFR

2012-07-01

...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Di-n-butyl phthalate 57 27 1,2-Dichlorobenzene 163 77 1,3-Dichlorobenzene 44 31 1,4-Dichlorobenzene... phthalate 203 81 2,4-Dimethylphenol 36 18 Dimethyl phthalate 47 19 4,6-Dinitro-o-cresol 277 78 2,4...

40 CFR 414.91 - Toxic pollutant effluent limitations and standards for direct discharge point sources that use...

Code of Federal Regulations, 2014 CFR

2014-07-01

...(k)fluoranthene 59 22 Benzo(a)pyrene 61 23 Bis(2-ethylhexyl) phthalate 279 103 Carbon Tetrachloride... Di-n-butyl phthalate 57 27 1,2-Dichlorobenzene 163 77 1,3-Dichlorobenzene 44 31 1,4-Dichlorobenzene... phthalate 203 81 2,4-Dimethylphenol 36 18 Dimethyl phthalate 47 19 4,6-Dinitro-o-cresol 277 78 2,4...

40 CFR 414.101 - Toxic pollutant effluent limitations and standards for direct discharge point sources that do not...

Code of Federal Regulations, 2012 CFR

2012-07-01

...(k)fluoranthene 47 19 Benzo(a)pyrene 48 20 Bis(2-ethylhexyl) phthalate 258 95 Carbon Tetrachloride... phthalate 43 20 1,2-Dichlorobenzene 794 196 1,3-Dichlorobenzene 380 142 1,4-Dichlorobenzene 380 142 1,1...-Dichloropropane 794 196 1,3-Dichloropropylene 794 196 Diethyl phthalate 113 46 2,4-Dimethylphenol 47 19 Dimethyl...

40 CFR 414.101 - Toxic pollutant effluent limitations and standards for direct discharge point sources that do not...

Code of Federal Regulations, 2014 CFR

2014-07-01

...(k)fluoranthene 47 19 Benzo(a)pyrene 48 20 Bis(2-ethylhexyl) phthalate 258 95 Carbon Tetrachloride... phthalate 43 20 1,2-Dichlorobenzene 794 196 1,3-Dichlorobenzene 380 142 1,4-Dichlorobenzene 380 142 1,1...-Dichloropropane 794 196 1,3-Dichloropropylene 794 196 Diethyl phthalate 113 46 2,4-Dimethylphenol 47 19 Dimethyl...

ACB-PCR MEASUREMENT OF K-RAS CODON 12 MUTATION IN A/J MOUSE LUNG EXPOSED TO BENZO[A]PYRENE: A DOSE-RESPONSE ASSESSMENT

EPA Science Inventory

Benzo[a]pyrene (B[a]P) is a known human carcinogen and environmental contaminant. The direct measurement of K-Ras mutant fraction (MF) was developed as a metric with which to examine the default assumption of low dose linearity in the mutational response to B...

Purification and partial characterization of peroxidase from human term placenta of non-smokers: metabolism of benzo(a)pyrene-7, 8-dihydrodiol.

PubMed

Madhavan, N D; Naidu, K A

2000-01-01

Peroxidase (Donor: H(2)O(2)oxidoreductase EC 1.11.1.7) from human term placentae of non-smokers was purified to homogeneity by a combination of NH(4)Cl extraction, affinity chromatography, (NH(4))(2)SO(4)precipitation, ion-exchange and gel filtration chromatography. The homogeneity of purified human placental peroxidase (HTPP) was confirmed by gel filtration, reverse phase high performance liquid chromatography (HPLC) and SDS-PAGE. Peroxidase was found to be a membrane bound enzyme. A high concentration of NH(4)Cl (1.2 m) was needed to extract and solublize the enzyme. Removal of the salt resulted in irreversible precipitation of the enzyme. The protein exhibited a molecular mass of 126 000 kDa according to gel filtration and approximately 60 000 kDa by SDS-PAGE, indicating that the peroxidase is a homodimer. The purified peroxidase showed an optimum pH range of 7 to 8.5 and the K(m)for H(2)O(2)and guaiacol were found to be 0.08 m m and 10.0 m m, respectively. The purified peroxidase oxidized several substrates, namely potassium iodide, tetramethyl benzidine, guaiacol, ortho dianisidne and tyrosine. The enzyme was resistant to thermal denaturation up to 70 degrees C and also to chaotropic agents, guanidinium chloride and urea. Spectral properties indicated the presence of Soret band at 433 which shifted to 451 nm on complexation with cyanide. The circular dichroism studies showed that HTPP has a predominantly helical secondary structure. The enzyme showed similarities to the myeloperoxidase with regard to spectral and catalytical properties but differed significantly in amino acid composition, the R(z)value and molecular mass. Purified HTPP differed from eosinophil peroxidase in all physico-chemical properties indicating that it is not of eosinophil origin, but may represent a distinct, constitutive peroxidase in human placenta. Further, purified peroxidase catalyzed oxidation of benzo(a)pyrene-7, 8-dihydrodiol in presence of tyrosine and hydrogen peroxide to BP-tetrols, the hydrolytic products of BP-diol-epoxides, demonstrating the ability of peroxidase in bioactivation of benzo(a)pyrene in human placenta. Copyright 2000 Harcourt Publishers Ltd.

Black raspberry extracts inhibit benzo(a)pyrene diol-epoxide-induced activator protein 1 activation and VEGF transcription by targeting the phosphotidylinositol 3-kinase/Akt pathway.

PubMed

Huang, Chuanshu; Li, Jingxia; Song, Lun; Zhang, Dongyun; Tong, Qiangsong; Ding, Min; Bowman, Linda; Aziz, Robeena; Stoner, Gary D

2006-01-01

Previous studies have shown that freeze-dried black raspberry extract fractions inhibit benzo(a)pyrene [B(a)P]-induced transformation of Syrian hamster embryo cells and benzo(a)pyrene diol-epoxide [B(a)PDE]-induced activator protein-1 (AP-1) activity in mouse epidermal Cl 41 cells. The phosphotidylinositol 3-kinase (PI-3K)/Akt pathway is critical for B(a)PDE-induced AP-1 activation in mouse epidermal Cl 41 cells. In the present study, we determined the potential involvement of PI-3K and its downstream kinases on the inhibition of AP-1 activation by black raspberry fractions, RO-FOO3, RO-FOO4, RO-ME, and RO-DM. In addition, we investigated the effects of these fractions on the expression of the AP-1 target genes, vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Pretreatment of Cl 41 cells with fractions RO-F003 and RO-ME reduced activation of AP-1 and the expression of VEGF, but not iNOS. In contrast, fractions RO-F004 and RO-DM had no effect on AP-1 activation or the expression of either VEGF or iNOS. Consistent with inhibition of AP-1 activation, the RO-ME fraction markedly inhibited activation of PI-3K, Akt, and p70 S6 kinase (p70(S6k)). In addition, overexpression of the dominant negative PI-3K mutant delta p85 reduced the induction of VEGF by B(a)PDE. It is likely that the inhibitory effects of fractions RO-FOO3 and RO-ME on B(a)PDE-induced AP-1 activation and VEGF expression are mediated by inhibition of the PI-3K/Akt pathway. In view of the important roles of AP-1 and VEGF in tumor development, one mechanism for the chemopreventive activity of black raspberries may be inhibition of the PI-3K/Akt/AP-1/VEGF pathway.

Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siddens, Lisbeth K.; Larkin, Andrew; Superfund Research Center, Oregon State University

2012-11-01

The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did notmore » differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by {sup 32}P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique pattern of gene alterations compared to BaP and PAH mixtures.« less

Functional Categorization of Transcriptome in the Species Symphysodon aequifasciatus Pellegrin 1904 (Perciformes: Cichlidae) Exposed to Benzo[a]pyrene and Phenanthrene

PubMed Central

Lemgruber, Renato de Souza Pinto; Marshall, Nislanha Ana dos Anjos; Ghelfi, Andrea; Fagundes, Daniel Barros; Val, Adalberto Luis

2013-01-01

This study aims to evaluate the transcriptome alterations, through cDNA libraries, associated with the combined effects of two PAHs, benzo[a]pyrene (0.5 µg/L) and phenanthrene (50 µg/L), present in crude oil, on specimens of Symphysodon aequifasciatus (discus fish) after 48 h of exposure. The cDNA libraries were constructed according to the SOLiD™ SAGE™ protocol for sequencing in the SOLiD v.3 Plus sequencer. The results were analyzed by bioinformatics and differentially expressed genes were categorized using the gene ontology program. The functional categories (terms) found in the gene ontology and the gene network generated using STRING software were used to predict the adverse effects of benzo[a]pyrene and phenanthrene in the liver. In the present study, 27,127 genes (compared to Danio rerio database) were identified. Considering only those genes with a p-value less than or equal to 0.05 and greater than or equal to two-fold change in expression across libraries, we found 804 genes, 438 down-regulated (54%) and 366 up-regulated (46%), in the experimental group compared to the control. Out of this total, 327 genes were successfully categorized, 174 down-regulated and 153 up-regulated, using gene ontology. Using String, the gene network was composed by 199 nodes, 124 of them resulting in 274 interactions. The results showed that even an acute exposure of 48 h caused metabolic change in response to environmental contaminants, resulting in changes of cell integrity, in oxidation-reduction processes, in the immune response and disturbances of intracellular signaling of discus fish. Also the gene network has showed no central interplay cluster, exhibiting instead interconnected clusters interactions and connected sub-networks. These findings highlight that even an acute sublethal exposure of PAHs can cause metabolism changes that may affect survival of discus. Our findings using SOLiD coupled with SAGE-method resulted in a powerful and reliable means for gene expression analysis in discus, a non-model Amazonian fish. PMID:24312524

Preliminary physiologically based pharmacokinetic models for benzo[a]pyrene and dibenzo[def,p]chrysene in rodents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crowell, Susan Ritger, E-mail: Susan.crowell@pnnl.gov; Amin, Shantu G.; Anderson, Kim A.

2011-12-15

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated as byproducts of natural and anthropogenic combustion processes. Despite significant public health concern, physiologically based pharmacokinetic (PBPK) modeling efforts for PAHs have so far been limited to naphthalene, plus simpler PK models for pyrene, nitropyrene, and benzo[a]pyrene (B[a]P). The dearth of published models is due in part to the high lipophilicity, low volatility, and myriad metabolic pathways for PAHs, all of which present analytical and experimental challenges. Our research efforts have focused upon experimental approaches and initial development of PBPK models for the prototypic PAH, B[a]P, and the more potent, albeitmore » less studied transplacental carcinogen, dibenzo[def,p]chrysene (DBC). For both compounds, model compartments included arterial and venous blood, flow limited lung, liver, richly perfused and poorly perfused tissues, diffusion limited fat, and a two compartment theoretical gut (for oral exposures). Hepatic and pulmonary metabolism was described for both compounds, as were fractional binding in blood and fecal clearance. Partition coefficients for parent PAH along with their diol and tetraol metabolites were estimated using published algorithms and verified experimentally for the hydroxylated metabolites. The preliminary PBPK models were able to describe many, but not all, of the available data sets, comprising multiple routes of exposure (oral, intravenous) and nominal doses spanning several orders of magnitude. Supported by Award Number P42 ES016465 from the National Institute of Environmental Health Sciences. -- Highlights: Black-Right-Pointing-Pointer We present PBPK models for benzo[a]pyrene (B[a]P) and dibenzo[def,p]chrysene (DBC). Black-Right-Pointing-Pointer B[a]P model accurately predicts data from multiple sources over a wide dose range. Black-Right-Pointing-Pointer DBC model was based on the B[a]P model as less chemical specific data is available. Black-Right-Pointing-Pointer DBC model accurately predicted preliminary pharmacokinetic data. Black-Right-Pointing-Pointer DBC model underscored data gaps on metabolism, binding and pharmacokinetics.« less

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase Imore » metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in this paper in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 μM), and higher intrinsic clearance at lower substrate concentrations (<0.07 μM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Finally, kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.« less

p53 Mutagenesis by Benzo[a]pyrene derived Radical Cations

PubMed Central

Sen, Sushmita; Bhojnagarwala, Pratik; Francey, Lauren; Lu, Ding; Jeffrey Field, Trevor M. Penning

2013-01-01

Benzo[a]pyrene (B[a]P), a major human carcinogen in combustion products such as cigarette smoke and diesel exhaust, is metabolically activated into DNA-reactive metabolites via three different enzymatic pathways. The pathways are the anti-(+)-benzo[a]pyrene 7,8-diol 9, 10-epoxide pathway (P450/ epoxide hydrolase catalyzed) (B[a]PDE), the benzo[a]pyrene o-quinone pathway (aldo ketose reductase (AKR) catalyzed) and the B[a]P radical cation pathway (P450 peroxidase catalyzed). We used a yeast p53 mutagenesis system to assess mutagenesis by B[a]P radical cations. Because radical cations are short-lived, they were generated in situ by reacting B[a]P with cumene hydroperoxide (CuOOH) and horse radish peroxidase (HRP) and then monitoring the generation of the more stable downstream products, B[a]P-1,6-dione and B[a]P-3,6-dione. Based on the B[a]P-1,6 and 3,6-dione formation, approximately 4µM of radical cation was generated. In the mutagenesis assays, the radical cations produced in situ showed a dose-dependent increase in mutagenicity from 0.25 µM to 10 µM B[a]P with no significant increase seen with further escalation to 50 µM B[a]P. However, mutagenesis was 200-fold less than with the AKR pathway derived B[a]P, 7–8 dione. Mutant p53 plasmids, which yield red colonies, were recovered from the yeast to study the pattern and spectrum of mutations. The mutation pattern observed was G to T (31%) > G to C (29%) > G to A (14%). The frequency of codons mutated by the B[a]P radical cations was essentially random and not enriched at known cancer hotspots. The quinone products of radical cations, B[a]P-1,6-dione and B[a]P-3,6-dione were more mutagenic than the radical cation reactions, but still less mutagenic than AKR derived B[a]P-7,8-dione. We conclude that B[a]P radical cations and their quinone products are weakly mutagenic in this yeast-based system compared to redox cycling PAH o-quinones. PMID:22768918

Molecular cloning and sequence analysis of heat shock proteins 70 (HSP70) and 90 (HSP90) and their expression analysis when exposed to benzo(a)pyrene in the clam Ruditapes philippinarum.

PubMed

Liu, Tong; Pan, Luqing; Cai, Yuefeng; Miao, Jingjing

2015-01-25

HSP70 and HSP90 are the most important heat shock proteins (HSPs), which play the key roles in the cell as molecular chaperones and may involve in metabolic detoxification. The present research has obtained full-length cDNAs of genes HSP70 and HSP90 from the clam Ruditapes philippinarum and studied the transcriptional responses of the two genes when exposed to benzo(a)pyrene (BaP). The full-length RpHSP70 cDNA was 2336bp containing a 5' untranslated region (UTR) of 51bp, a 3' UTR of 335bp and an open reading frame (ORF) of 1950bp encoding 650 amino acid residues. The full-length RpHSP90 cDNA was 2839bp containing a 107-bp 5' UTR, a 554-bp 3' UTR and a 2178-bp ORF encoding 726 amino acid residues. The deduced amino acid sequences of RpHSP70 and RpHSP90 shared the highest identity with the sequences of Paphia undulata, and the phylogenetic trees showed that the evolutions of RpHSP70 and RpHSP90 were almost in accord with the evolution of species. The RpHSP70 and RpHSP90 mRNA expressions were detected in all tested tissues in the adult clams (digestive gland, gill, adductor muscle and mantle) and the highest mRNA expression level was observed in the digestive gland compared to other tissues. Quantitative real-time RT-PCR analysis revealed that mRNA expression levels of the clam RpHSP70, RpHSP90 and other xenobiotic metabolizing enzymes (XMEs) (AhR, DD, GST, GPx) in the digestive gland of R. philippinarum were induced by benzo(a)pyrene (BaP) and the absolute expression levels of these genes showed a temporal and dose-dependent response. The results suggested that RpHSP70 and RpHSP90 were involved in the metabolic detoxification of BaP in the clam R. philippinarum. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

DOE PAGES

Smith, Jordan N.; Mehinagic, Denis; Nag, Subhasree; ...

2017-01-21

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase Imore » metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in this paper in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 μM), and higher intrinsic clearance at lower substrate concentrations (<0.07 μM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Finally, kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.« less

Influence of dietary fat type on benzo(a)pyrene [B(a)P] biotransformation in a B(a)P-induced mouse model of colon cancer

PubMed Central

Diggs, Deacqunita L.; Myers, Jeremy N.; Banks, Leah D.; Niaz, Mohammad S.; Hood, Darryl B.; Roberts, L. Jackson; Ramesh, Aramandla

2013-01-01

In the US alone, around 60,000 lives/year are lost due to colon cancer. Diet and environment have been implicated in the development of sporadic colon tumors. The objective of this study was to determine how dietary fat potentiates the development of colon tumors through altered B(a)P biotransformation, using the Adenomatous polyposis coli with Multiple intestinal neoplasia mouse model. Benzo(a)pyrene was administered to mice through tricaprylin, and unsaturated (USF; peanut oil) and saturated (SF; coconut oil) fats at doses of 50 and 100 μg/kg via oral gavage over a 60-day period. Blood, colon, and liver were collected at the end of exposure period. The expression of B(a)P biotransformation enzymes [cytochrome P450 (CYP)1A1, CYP1B1 and glutathione-S-transferase] in liver and colon were assayed at the level of protein, mRNA and activities. Plasma and tissue samples were analyzed by reverse phase high-performance liquid chromatography for B(a)P metabolites. Additionally, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Benzo(a)pyrene exposure through dietary fat altered its metabolic fate in a dose-dependent manner, with 100 μg/kg dose group registering an elevated expression of B(a)P biotransformation enzymes, and greater concentration of B(a)P metabolites, compared to the 50 μg/kg dose group (P<.05). This effect was more pronounced for SF group compared to USF group (P<.05). These findings establish that SF causes sustained induction of B(a)P biotransformation enzymes and extensive metabolism of this toxicant. As a consequence, B(a)P metabolites were generated to a greater extent in colon and liver, whose concentrations also registered a dose-dependent increase. These metabolites were found to bind with DNA and form B(a)P-DNA adducts, which may have contributed to colon tumors in a subchronic exposure regimen. PMID:24231098

Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens.

PubMed

Nagabhushan, M; Amonkar, A J; D'Souza, A V; Bhide, S V

1987-01-01

Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.

40 CFR 421.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... (c) Subpart (B)—Anode Bake Plant Wet Air Pollution Control (Closed Top Ring Furnace). BAT Effluent... per million pounds) of anodes baked Benzo(a)pyrene 0.146 0.067 Antimony 8.346 3.719 Nickel 2.378 1.600 Aluminum 26.420 11.720 Fluoride 257.300 114.200 (d) Subpart B—Anode Bake Plant Wet Air Pollution Control...

40 CFR 421.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2014 CFR

2014-07-01

... (c) Subpart (B)—Anode Bake Plant Wet Air Pollution Control (Closed Top Ring Furnace). BAT Effluent... per million pounds) of anodes baked Benzo(a)pyrene 0.146 0.067 Antimony 8.346 3.719 Nickel 2.378 1.600 Aluminum 26.420 11.720 Fluoride 257.300 114.200 (d) Subpart B—Anode Bake Plant Wet Air Pollution Control...

40 CFR 421.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2013 CFR

2013-07-01

... (c) Subpart (B)—Anode Bake Plant Wet Air Pollution Control (Closed Top Ring Furnace). BAT Effluent... per million pounds) of anodes baked Benzo(a)pyrene 0.146 0.067 Antimony 8.346 3.719 Nickel 2.378 1.600 Aluminum 26.420 11.720 Fluoride 257.300 114.200 (d) Subpart B—Anode Bake Plant Wet Air Pollution Control...

40 CFR 421.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2012 CFR

2012-07-01

... (c) Subpart (B)—Anode Bake Plant Wet Air Pollution Control (Closed Top Ring Furnace). BAT Effluent... per million pounds) of anodes baked Benzo(a)pyrene 0.146 0.067 Antimony 8.346 3.719 Nickel 2.378 1.600 Aluminum 26.420 11.720 Fluoride 257.300 114.200 (d) Subpart B—Anode Bake Plant Wet Air Pollution Control...

40 CFR 421.23 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... (c) Subpart (B)—Anode Bake Plant Wet Air Pollution Control (Closed Top Ring Furnace). BAT Effluent... per million pounds) of anodes baked Benzo(a)pyrene 0.146 0.067 Antimony 8.346 3.719 Nickel 2.378 1.600 Aluminum 26.420 11.720 Fluoride 257.300 114.200 (d) Subpart B—Anode Bake Plant Wet Air Pollution Control...

Environmental Pollutant Benzo[a]Pyrene Impacts the Volatile Metabolome and Transcriptome of the Human Gut Microbiota

PubMed Central

Defois, Clémence; Ratel, Jérémy; Denis, Sylvain; Batut, Bérénice; Beugnot, Réjane; Peyretaillade, Eric; Engel, Erwan; Peyret, Pierre

2017-01-01

Benzo[a]pyrene (B[a]P) is a ubiquitous, persistent, and carcinogenic pollutant that belongs to the large family of polycyclic aromatic hydrocarbons. Population exposure primarily occurs via contaminated food products, which introduces the pollutant to the digestive tract. Although the metabolism of B[a]P by host cells is well known, its impacts on the human gut microbiota, which plays a key role in health and disease, remain unexplored. We performed an in vitro assay using 16S barcoding, metatranscriptomics and volatile metabolomics to study the impact of B[a]P on two distinct human fecal microbiota. B[a]P exposure did not induce a significant change in the microbial structure; however, it altered the microbial volatolome in a dose-dependent manner. The transcript levels related to several metabolic pathways, such as vitamin and cofactor metabolism, cell wall compound metabolism, DNA repair and replication systems, and aromatic compound metabolism, were upregulated, whereas the transcript levels related to the glycolysis-gluconeogenesis pathway and bacterial chemotaxis toward simple carbohydrates were downregulated. These primary findings show that food pollutants, such as B[a]P, alter human gut microbiota activity. The observed shift in the volatolome demonstrates that B[a]P induces a specific deviation in the microbial metabolism. PMID:28861070

Benzo[a]pyrene exposure increases toxic biomarkers and morphological disorders in mouse cervix.

PubMed

Gao, Meili; Li, Yongfei; Sun, Ying; Shah, Walayat; Yang, Shuiyun; Wang, Yili; Long, Jiangang

2011-11-01

Benzo[a]pyrene (BaP) is a representative compound of polycyclic aromatic hydrocarbons exerting cytotoxicity and genotoxicity in the human liver, lung, stomach and skin. However, the toxic effect of BaP on cervical tissue remains unclear. This study was carried out to investigate the toxic effects of BaP on the cervix of ICR mice. Female mice were treated with BaP by intraperitoneal injection and oral gavage at a dose of 2.5, 5 and 10 mg/kg body-weight, twice a week for 14 weeks. BaP treatment caused a significant increase in the levels of MDA and IL-6 with significantly increased activity of CYP1A1, creatine kinase and aspartate aminotransferase (AST) and decreased activity of glutathione-S-transferase in the cervix and liver. The relative cervix weight was markedly reduced in the intraperitoneal BaP injection groups, whereas only a slight reduction was observed in the oral gavage groups. The increase in weight decreased with increasing BaP dose. Moreover, BaP treatment induced significant pathomorphological changes in the cervical tissue and increased the mortality of the mice. Taken together, these results suggest that BaP causes a certain toxic effect on cervical tissue. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

The effect of occupational exposure to benzo[a]pyrene on neurobehavioral function in coke oven workers.

PubMed

Qiu, Chongying; Peng, Bin; Cheng, Shuqun; Xia, Yinyin; Tu, Baijie

2013-03-01

Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (B[a]P), known as an indicator species for PAH contamination, is a neurobehavioral toxicant. The purpose of the study was to evaluate the relationship between B[a]P exposure, a B[a]P-related urinary metabolite and neurobehavioral function among coke oven workers. Coke oven workers and oxygen factory workers participated in this study. B[a]P exposure was monitored by air sampling pump, and urinary 1-hydroxypyrene (1-OHP) level was detected with high performance liquid chromatography (HPLC). A questionnaire and the neurobehavioral core test battery (NCTB) were administered to all subjects. B[a]P-exposed workers were found to have higher urinary 1-OHP levels and worse NCTB performances on eight items than control workers. B[a]P concentrations were higher in the coke oven plant than that in the controls' workplace. The performances on simple reaction time, correct pursuit aiming, and error pursuit aiming decreased with increasing airborne B[a]P in coke oven workers. There were significant correlations between urinary 1-OHP level and six items of the NCTB. Occupational exposure to B[a]P is associated with neurobehavioral function impairment in coke oven workers. Copyright © 2012 Wiley Periodicals, Inc.

Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers.

PubMed Central

Harris, C C; Vahakangas, K; Newman, M J; Trivers, G E; Shamsuddin, A; Sinopoli, N; Mann, D L; Wright, W E

1985-01-01

Coke oven workers are exposed to high levels of carcinogenic polycyclic aromatic hydrocarbons, including benzo[a]pyrene (B[a]P), and are at increased risk of lung cancer. Since B[a]P is enzymatically activated to 7 beta,8 alpha-dihydroxy(9 alpha, 10 alpha)epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE) that forms adducts with DNA, the presence of these adducts was measured in DNA from peripheral blood lymphocytes by synchronous fluorescence spectrophotometry and enzyme radioimmunoassay. Approximately two-thirds of the workers had detectable levels of B[a]PDE-DNA adducts. Antibodies to the DNA adducts were also found in the serum of 27% of the workers. B[a]PDE-DNA adducts were not detectable in lymphocytes and antibodies to the adducts were not detected in sera from a control group of nonsmoking laboratory workers. DNA adducts and/or antibodies to the adducts indicate exposure to B[a]P and its metabolic activation to the carcinogenic metabolite that covalently binds to and damages DNA. Detection of adducts and antibodies to them may also be useful as internal dosimeters of the pathobiological effective doses of chemical carcinogens. PMID:2413443

Interaction of benzo[a]pyrene diol epoxide isomers with human serum albumin: Site specific characterisation of adducts and associated kinetics

NASA Astrophysics Data System (ADS)

Motwani, Hitesh V.; Westberg, Emelie; Törnqvist, Margareta

2016-11-01

Carcinogenicity of benzo[a]pyrene {B[a]P, a polycyclic aromatic hydrocarbon (PAH)} involves DNA-modification by B[a]P diol epoxide (BPDE) metabolites. Adducts to serum albumin (SA) are not repaired, unlike DNA adducts, and therefore considered advantageous in assessment of in vivo dose of BPDEs. In the present work, kinetic experiments were performed in relation to the dose (i.e. concentration over time) of different BPDE isomers, where human SA (hSA) was incubated with respective BPDEs under physiological conditions. A liquid chromatography (LC) tandem mass spectrometry methodology was employed for characterising respective BPDE-adducts at histidine and lysine. This strategy allowed to structurally distinguish between the adducts from racemic anti- and syn-BPDE and between (+)- and (-)-anti-BPDE, which has not been attained earlier. The adduct levels quantified by LC-UV and the estimated rate of disappearance of BPDEs in presence of hSA gave an insight into the reactivity of the diol epoxides towards the N-sites on SA. The structure specific method and dosimetry described in this work could be used for accurate estimation of in vivo dose of the BPDEs following exposure to B[a]P, primarily in dose response studies of genotoxicity, e.g. in mice, to aid in quantitative risk assessment of PAHs.

Mechanism-based inactivation of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity by acetylenic and olefinic polycyclic arylhydrocarbons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, L.S.

A series of aryl acetylenes and aryl olefins have been examined as substrates and inhibitors of cytochrome P-450 dependent monooxygenases in liver microsomes from 5,6-benzoflavone or phenobarbital pretreated rats. 1-Ethynylpyrene (EP), 3-ethynylperylene (EPL), cis- and trans-1-(2-bromo-vinyl)pyrene (c-BVP and t-BVP), and 1-allylpyrene (AP) serve as mechanism-based irreversible inactivators (suicide inhibitors) of benzo(a)pyrene (BP) hydroxylase, while 1-vinyl-pyrene (VP) and phenyl 1-pyrenyl acetylene (PPA) do not cause a detectable suicide inhibition of the BP hydroxylase. The mechanism-based loss of BP hydroxylase activity caused by the aryl acetylenes is not accompanied by a corresponding loss of the P-450 content of the microsomes. In themore » presence of NADPH, /sup 3/H-labeled EP covalently attached to P-450 isozymes with a measured stoichiometry of one mole of EP per mole of the P-450 heme. The results of the effects of these aryl derivatives in the mammalian cell-mediated mutagenesis assay and toxicity assay show that none of the compounds examined nor any of the their metabolites produced in the incubation system are cytotoxic to V79 cells.« less

Evolution of potential ecological impacts of the bottom sediment from the Gulf of Gemlik; Marmara Sea, Turkey.

PubMed

Unlü, Selma; Alpar, Bedri

2009-12-01

The eastern and southern coasts of the Gulf of Gemlik, a resort in the Sea of Marmara, Turkey, are under the influence of rapid ecotourism development, direct domestic and industrial discharges via rivers and outfalls, surface run-off, drainage from ports and shipping. According to sediment quality criteria in use around the world, sediment quality in the gulf shows a broad spectrum. It is more related by direct input, rather than by the type of sediment, and excluding inner port and southern coasts, it does not exert adverse biological effects yet. The total PAH concentrations range from 51 to 13,482 ng/g dry weight with the mean value of 1,850 ng/g dry weight (n = 61). The elevated values of the total toxic Benzo[a]pyrene equivalency (TEQcarc), with a maximum of 1,838 ng/g dry weight, were found at the inner harbor of Gemlik, possibly posing hazard to benthic organisms. Among the different PAHs, the contribution to the total TEQcarc decreased as the following order: Benzo[a]pyrene (43.6%) > Benzo[k]fluoranthene (36.0%) > Indeno[1,2,3-cd]pyrene (35.1%) > Benzo[b]fluoranthene (20.0%) > Chrysene + Triphenylene (18.9%) > Benzo[a]anthracene (12.5%).

The role of water ventilation and sediment ingestion in the uptake of benzo[A]pyrene in gizzard shad (Dorosoma cepedianum)

USGS Publications Warehouse

Kolok, Alan; Huckins, James N.; Petty, Jimmie D.; Oris, James T.

1996-01-01

The objective of this study was to determine whether sediment ingestion or water ventilation was the primary route of uptake for benzo[a]pyrene (BaP) in the gizzard shad (Dorosoma cepedianum), a detritivorous fish. Two experiments were conducted in which fish were exposed to sediments spiked with 1 μg/g BaP. In the first experiment, fish were prevented from feeding by esophagus ligation. In the second experiment, 20 nonligated fish and 30 ligated fish were added to the aquarium. The nonligated fish roiled the water as they fed. Fish were collected 4, 8, 15, and 22 d after the experiments began. Gizzard shad metabolize BaP; therefore, the concentrations of BaP equivalents (parent BaP plus metabolite) were determined. Concentrations of BaP equivalents were significantly greater in the ligated fish in experiment 2 relative to those in experiment 1. In contrast, the concentration of BaP equivalents in the ligated fish in experiment 2 was not significantly different than that in the nonligated fish. Our results suggest that ventilation of turbid water may be a significant source of BaP for gizzard shad. Sediment ingestion, however, does not appear to significantly influence the total body concentration of BaP equivalents in gizzard shad.

Combined ultrasound with Fenton treatment for the degradation of carcinogenic polycyclic aromatic hydrocarbons in textile dying sludge.

PubMed

Zhang, Jian-Hao; Zou, Hai-Yuan; Ning, Xun-An; Lin, Mei-Qing; Chen, Chang-Min; An, Tai-Cheng; Sun, Jian

2017-03-22

To develop an effective method to remove the toxic and carcinogenic polycyclic aromatic hydrocarbons (CPAHs) from textile dyeing sludge, five CPAHs were selected to investigate the degradation efficiencies using ultrasound combined with Fenton process (US/Fenton). The results showed that the synergistic effect of the US/Fenton process on the degradation of CPAHs in textile dyeing sludge was significant with the synergy degree of 30.4. During the US/Fenton process, low ultrasonic density showed significant advantage in degrading the CPAHs in textile dyeing sludge. Key reaction parameters on CPAHs degradation were optimized by the central composite design as followed: H 2 O 2 concentration of 152 mmol/L, ultrasonic density of 408 W/L, pH value of 3.7, the molar ratio of H 2 O 2 to Fe 2+ of 1.3 and reaction time of 43 min. Under the optimal conditions of the US/Fenton process, the degradation efficiencies of five CPAHs were obtained as 81.23% (benzo[a]pyrene) to 84.98% (benz[a]anthracene), and the benzo[a]pyrene equivalent (BaP eq ) concentrations of five CPAHs declined by 81.22-85.19%, which indicated the high potency of US/Fenton process for removing toxic CPAHs from textile dyeing sludge.

Impact of plant photosystems in the remediation of benzo[a]pyrene and pyrene spiked soils.

PubMed

Sivaram, Anithadevi Kenday; Logeshwaran, Panneerselvan; Lockington, Robin; Naidu, Ravi; Megharaj, Mallavarapu

2018-02-01

The phytoremediation potential of 14 different plant species belonging to C3 and C4 carbon fixation pathway for soils spiked with polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (B[a]P) and pyrene (PYR) was investigated. A glasshouse experiment was conducted to measure the changes in morphological, physiological, biochemical parameters and the bioaccumulation and biodegradation ability of the plants in soils spiked with 48 and 194 mg kg -1 of B[a]P and PYR, respectively. The per cent removal efficacy of B[a]P and PYR by the tested plant species over a period of 50 days was from 6 to 26% and 14 to 40% respectively. The maximum removal of both B[a]P and PYR was observed in Sudan grass (C4), vetiver (C4), maize (C4), and sunflower (C3). In terms of accumulation in root and shoot, the concentration of PYR was higher in both C3 and C4 plant species when compared to B[a]P. Overall the results indicated that C4 plants were more efficient than their C3 counterparts in terms of morphological, physiological, biochemical and degradation ability of PAHs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mouth-Level Intake of Benzo[a]pyrene from Reduced Nicotine Cigarettes

PubMed Central

Ding, Yan S.; Ward, Jennye; Hammond, David; Watson, Clifford H.

2014-01-01

Cigarette smoke is a known source of exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), especially benzo[a]pyrene (BaP). Exposure to BaP in cigarette smoke is influenced by how a person smokes and factors, such as tobacco blend. To determine whether sustained use of reduced-nicotine cigarettes is associated with changes in exposure to nicotine and BaP, levels of BaP in spent cigarette filter butts were correlated with levels of BaP in cigarette smoke to estimate mouth-level intake (MLI) of BaP for 72 daily smokers given three progressively reduced nicotine content cigarettes. Urinary cotinine, a marker of nicotine exposure, and urinary 1-hydroxypyrene (1-HOP), a marker of PAH exposure, were measured throughout the study. Median daily BaP MLI and urine cotinine decreased in a similar manner as smokers switched to progressively lower nicotine cigarettes, despite relatively constant daily cigarette consumption. 1-HOP levels were less responsive to the use of reduced nicotine content cigarettes. We demonstrate that spent cigarette filter butt analysis is a promising tool to estimate MLI of harmful chemicals on a per cigarette or per-day basis, which partially addresses the concerns of the temporal influence of smoking behavior or differences in cigarette design on exposure. PMID:25411724

Biotransformation of benzo[a]pyrene by the thermophilic bacterium Bacillus licheniformis M2-7.

PubMed

Guevara-Luna, Joseph; Alvarez-Fitz, Patricia; Ríos-Leal, Elvira; Acevedo-Quiroz, Macdiel; Encarnación-Guevara, Sergio; Moreno-Godinez, Ma Elena; Castellanos-Escamilla, Mildred; Toribio-Jiménez, Jeiry; Romero-Ramírez, Yanet

2018-06-09

Benzo[a]pyrene (BaP) is recognized as a potentially carcinogenic and mutagenic hydrocarbon, and thus, its removal from the environment is a priority. The use of thermophilic bacteria capable of biodegrading or biotransforming this compound to less toxic forms has been explored in recent decades, since it provides advantages compared to mesophilic organisms. This study assessed the biotransformation of BaP by the thermophilic bacterium Bacillus licheniformis M2-7. Our analysis of the biotransformation process mediated by strain M2-7 on BaP shows that it begins during the first 3 h of culture. The gas chromatogram of the compound produced shows a peak with a retention time of 17.38 min, and the mass spectra shows an approximate molecular ion of m/z 167, which coincides with the molecular weight of the chemical formula C 6 H 4 (COOH) 2 , confirming a chemical structure corresponding to phthalic acid. Catechol 2,3-dioxygenase (C23O) enzyme activity was detected in minimal saline medium supplemented with BaP (0.33 U mg -1 of protein). This finding suggests that B. licheniformis M2-7 uses the meta pathway for biodegrading BaP using the enzyme C23O, thereby generating phthalic acid as an intermediate.

Aliphatic and polycyclic aromatic hydrocarbons in the Xihe River, an urban river in China's Shenyang City: distribution and risk assessment.

PubMed

Guo, Wei; He, Mengchang; Yang, Zhifeng; Lin, Chunye; Quan, Xiangchun

2011-02-28

The characteristics of petroleum hydrocarbons and the risks they pose to the ecosystem were studied in the Xihe River, which is an urban river located in Shenyang, China. High levels of aliphatic hydrocarbons (AHc) and polycyclic aromatic hydrocarbons (PAHs) were observed in the river due to the discharge of wastewater from industrial and municipal facilities for a long period of time. High-molecular-weight hydrocarbons, including unresolved complex mixtures (UCM) of n-alkanes between n-C16 and n-C32 and of PAHs with four to six rings, were the dominant hydrocarbons in the river, particularly in suspended particulate matter (SPM) and sediments. The AHc was mainly from petrogenic sources, whereas PAHs was from both pyrolytic and petrogenic source inputs. Our results suggest that there is a high risk of toxicity for the soils and groundwater of the study area. The overall toxicity in the sediments can be described using the toxic equivalent (TEQ) of dibenzo[a,h]anthracene (DBA) based on benzo(a)pyrene (TEQ(BaP)) and dioxins (TEQ(TCDD)) toxic equivalent concentrations. The TEQ values for benzo(a)pyrene (TEQ(BaP)) and dioxins (TEQ(TCDD)) presented a consistent assessment of sediment PAHs. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Combination of Liquid Chromatography with Multivariate Curve Resolution-Alternating Least-Squares (MCR-ALS) in the Quantitation of Polycyclic Aromatic Hydrocarbons Present in Paprika Samples.

PubMed

Monago-Maraña, Olga; Pérez, Rocío L; Escandar, Graciela M; Muñoz de la Peña, Arsenio; Galeano-Díaz, Teresa

2016-11-02

This work presents a strategy for quantitating polycyclic aromatic hydrocarbons (PAHs) in smoked paprika samples. For this, a liquid chromatographic method with fluorimetric detection (HPLC-FLD) was optimized. To resolve some interference co-eluting with the target analytes, the second-order multivariate curve resolution-alternating least-squares (MCR-ALS) algorithm has been employed combined with this liquid chromatographic method. Among the eight PAHs quantified (fluorene, phenanthrene, anthracene, pyrene, chrysene, benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene) by HPLC-FLD, only in the case of fluorene, pyrene, and benzo[b]fluoranthene was it necessary to apply the second-order algorithm for their resolution. Limits of detection and quantitation were between 0.015 and 0.45 mg/kg and between 0.15 and 1.5 mg/kg, respectively. Good recovery results (>80%) for paprika were obtained via the complete extraction procedure, consisting of an extraction from the matrix and the cleanup of the extract by means of silica cartridges. Higher concentrations of chrysene, benzo[a]anthracene, benzo[b]fluoranthene, and benzo[a]pyrene were found in the paprika samples, with respect to the maximal amounts allowed for other spices that are under European Regulation (EU) N° 2015/1933.

[Expression of miR-21 and Its Acat1, Armcx1, and Pten Target Genes in Liver of Female Rats Treated with DDT and Benzo[a]pyrene].

PubMed

Chanyshev, M D; Ushakov, D S; Gulyaeva, L F

2017-01-01

MiR-21 is the most studied cancer-promoting oncomiR, which target numerous tumor suppressor genes associated with proliferation, apoptosis, and invasion. Here we have studied the synthesis of miR-21 and quantified the mRNA and protein levels for miR-21 potential target genes, i.e., Acat1, Armcx1, and Pten, in the livers of female Wistar rats after their treatment with either 1,1-trichloro-2,2-di(4-chlorophenyl)ethane (DDT) or benzo[a]pyrene (BP). The most important finding appears to be the significant decrease in the miR-21 level the day after treatment with DDT with subsequent rebound. These changes are accompanied by an increase and subsequent drop in the levels of mRNAs and proteins of the Acat1, Armcx1, and Pten genes. These observations indicate the involvement of miR-21 in the posttranscriptional regulation of the Acat1, Armcx1, and Pten genes in response to xenobiotics. We hypothesize that the toxic effects of xenobiotics may be indirect and may manifest by inducing epigenetic changes, particularly through the regulation of miRNAs and their target genes.

Electrochemistry coupled to (LC-)MS for the simulation of oxidative biotransformation reactions of PAHs.

PubMed

Wigger, Tina; Seidel, Albrecht; Karst, Uwe

2017-06-01

Electrochemistry coupled to liquid chromatography and mass spectrometry was used for simulating the biological and environmental fate of polycyclic aromatic hydrocarbons (PAHs) as well as for studying the PAH degradation behavior during electrochemical remediation. Pyrene and benzo[a]pyrene were selected as model compounds and oxidized within an electrochemical thin-layer cell equipped with boron-doped diamond electrode. At potentials of 1.2 and 1.6 V vs. Pd/H 2 , quinones were found to be the major oxidation products for both investigated PAHs. These quinones belong to a large group of PAH derivatives referred to as oxygenated PAHs, which have gained increasing attention in recent years due to their high abundance in the environment and their significant toxicity. Separation of oxidation products allowed the identification of two pyrene quinone and three benzo[a]pyrene quinone isomers, all of which are known to be formed via photooxidation and during mammalian metabolism. The good correlation between electrochemically generated PAH quinones and those formed in natural processes was also confirmed by UV irradiation experiments and microsomal incubations. At potentials higher than 2.0 V, further degradation of the initial oxidation products was observed which highlights the capability of electrochemistry to be used as remediation technique. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lipid metabolism and benzo[a]pyrene degradation by Fusarium solani: an unexplored potential.

PubMed

Delsarte, Isabelle; Rafin, Catherine; Mrad, Fida; Veignie, Etienne

2018-04-01

In a search for indigenous soil saprotrophic fungi for bioremediation purposes, Fusarium solani, a saprotrophic fungus belonging to the phylum Ascomycota, was isolated from a fossil carbon contaminated soil. The effect of the carbon source, glucose or olive oil, was investigated in vitro on the biomass produced by F. solani and on the degradation of benzo[a]pyrene (BaP) in mineral medium. After only 12 days of incubation, BaP degradation by F. solani was higher (37.4%) with olive oil used as the carbon source than the one obtained with glucose (4.2%). Catalase activity increased in the presence of olive oil (3.4 μkat mg -1 protein) in comparison with glucose (2.1 μkat mg -1 protein). When olive oil was used as the carbon source, BaP degradation increased up to 76.0% in the presence of a specific catalase inhibitor, 3-Amino-1,2,4-triazole (2 mM). This metabolic engineering strategy based both on the use of olive oil as carbon source (cultivation strategy) and on the blocking of the catalase activity could be an innovative and promising approach for fungal biodegradation of BaP and consequently for bioremediation of soil contaminated with polycyclic aromatic hydrocarbons.

Analysis of benzo[a]pyrene metabolites formed by rat hepatic microsomes using high pressure liquid chromatography: optimization of the method

PubMed Central

Moserová, Michaela; Kotrbová, Věra; Aimová, Dagmar; Šulc, Miroslav; Frei, Eva; Stiborová, Marie

2009-01-01

A simple and sensitive method was developed to separate the carcinogenic polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), and six of its oxidation metabolites generated by rat hepatic microsomes enriched with cytochrome P450 (CYP) 1A1, by high pressure liquid chromatography (HPLC). The HPLC method, using an acetonitrile/water gradient as mobile phase and UV detection, provided appropriate separation and detection of both mono- and di-hydroxylated metabolites of BaP as well as BaP diones formed by rat hepatic microsomes and the parental BaP. In this enzymatic system, 3-hydroxy BaP, 9-hydroxy BaP, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-9,10-dihydrodiol and BaP-dione were generated. Among them the mono-hydroxylated BaP metabolite, 3-hydroxy BaP followed by di-hydroxylated BaP products, BaP-7,8-dihydrodiol and BaP-9,10-dihydrodiol, predominated, while BaP-dione was a minor metabolite. This HPLC method will be useful for further defining the roles of the CYP1A1 enzyme with both in vitro and in vivo models in understanding its real role in activation and detoxification of BaP. PMID:21217860

Bioavailability of atrazine, pyrene and benzo[a]pyrene in European river waters

USGS Publications Warehouse

Akkanen, J.; Penttinen, S.; Haitzer, M.; Kukkonen, J.V.K.

2001-01-01

Thirteen river waters and one humic lake water were characterized. The effects of dissolved organic matter (DOM) on the bioavailability of atrazine, pyrene and benzo[a]pyrene (B[a]P) was evaluated. Binding of the chemicals by DOM was analyzed with the equilibrium dialysis technique. For each of the water samples, 24 h bioconcentration factors (BCFs) of the chemicals were measured in Daphnia magna. The relationship between DOM and other water characteristics (including conductivity, water hardness and pH), and bioavailability of the chemicals was studied by performing several statistical analyses, including multiple regression analyses, to determine how much of the variation of BCF values could be explained by the quantity and quality of DOM. The bioavailability of atrazine was not affected by DOM or any other water characteristics. Although equilibrium dialysis showed binding of pyrene to DOM, the bioavailability of pyrene was not significantly affected by DOM. The bioavailability of B[a]P was significantly affected by both the quality and quantity of DOM. Multiple regression analyses, using the quality (ABS270 and HbA%) and quantity of DOM as variables, explainedup to 70% of the variation in BCF of B[a]P in the waters studied. ?? 2001 Elsevier Science Ltd. All rights reserved.

Effects of particulate carbonaceous matter on the bioavailability of benzo[a]pyrene and 2,2‘,5,5‘-tetrachlorobiphenyl to the clam, Macoma balthica

USGS Publications Warehouse

McLeod, Pamela B.; van den Heuvel-Greve, Martine J.; Allen-King, Richelle M.; Luoma, Samuel N.; Luthy, Richard G.

2004-01-01

We investigated the bioavailability via diet of spiked benzo[a]pyrene (BaP) and 2,2‘,5,5‘-tetrachlorobiphenyl (PCB-52) from different carbonaceous (non-carbonate, carbon containing) particle types to clams (Macoma balthica) collected from San Francisco Bay. Our results reveal significant differences in absorption efficiency between compounds and among carbonaceous particle types. Absorption efficiency for PCB-52 was always greater than that for BaP bound to a given particle type. Among particles, absorption efficiency was highest from wood and diatoms and lowest from activated carbon. Large differences in absorption efficiency could not be simply explained by comparatively small differences in the particles' total organic carbon content. BaP and PCB-52 bound to activated carbon exhibited less than 2% absorption efficiency and were up to 60 times less available to clams than the same contaminants associated with other types of carbonaceous matter. These results suggest that variations in the amount and type of sediment particulate carbonaceous matter, whether naturally occurring or added as an amendment, will have a strong influence on the bioavailability of hydrophobic organic contaminants. This has important implications for environmental risk assessment, sediment management, and development of novel remediation techniques.

Effects of particulate carbonaceous matter on the bioavailability of benzo[a]pyrene and 2,2'5,5'-tetrachlorobiphenyl to the clam, Macoma balthica

USGS Publications Warehouse

McLeod, Pamela B.; van den Heuvel-Greve, Martine J.; Allen-King, Richelle M.; Luoma, Samuel N.; Luthy, Richard G.

2004-01-01

We investigated the bioavailability via diet of spiked benzo[a]pyrene (BaP) and 2,2‘,5,5‘-tetrachlorobiphenyl (PCB-52) from different carbonaceous (non-carbonate, carbon containing) particle types to clams (Macoma balthica) collected from San Francisco Bay. Our results reveal significant differences in absorption efficiency between compounds and among carbonaceous particle types. Absorption efficiency for PCB-52 was always greater than that for BaP bound to a given particle type. Among particles, absorption efficiency was highest from wood and diatoms and lowest from activated carbon. Large differences in absorption efficiency could not be simply explained by comparatively small differences in the particles' total organic carbon content. BaP and PCB-52 bound to activated carbon exhibited less than 2% absorption efficiency and were up to 60 times less available to clams than the same contaminants associated with other types of carbonaceous matter. These results suggest that variations in the amount and type of sediment particulate carbonaceous matter, whether naturally occurring or added as an amendment, will have a strong influence on the bioavailability of hydrophobic organic contaminants. This has important implications for environmental risk assessment, sediment management, and development of novel remediation techniques.

Polycyclic aromatic hydrocarbons in some grounded coffee brands.

PubMed

Grover, Inderpreet Singh; Sharma, Rashmi; Singh, Satnam; Pal, Bonamali

2013-08-01

Potentially toxic 16 priority polycyclic aromatic hydrocarbons (PAHs) were determined in four brands of grounded coffee. Four to 13 PAHs were detected. Concentrations of total PAHs in different brands of coffee samples were in the range of 831.7-1,589.7 μg/kg. Benzo[a]pyrene (2A: probable human carcinogen) was found in Nescafe Premium whereas naphthalene (2B: possible human carcinogen) was found in all the samples of coffee.

Preliminary Investigation of Wastewater-Related Contaminants Near Home Sewage Treatment Systems in Ohio

DTIC Science & Technology

2005-01-01

preservative, component of tar, diesel, or crude oil, CP Anthraquinone 0.5 Manuf dye/ textiles , seed treatment, bird repellant Benzo[a]pyrene 0.5...diethyl-meta-toluamide (Deet) 0.5 I, urban uses, mosquito repellent Naphthalene 0.5 Fumigant, moth repellent , major component (about 10%) of...UV, ultraviolet; --, no data] Compound name Laboratory reporting limit Possible compound uses or sources 1,4-Dichlorobenzene 0.5 Moth repellant

Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens.

PubMed

David, Rhiannon; Ebbels, Timothy; Gooderham, Nigel

2016-01-01

Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined. We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar). Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry. Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair. Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88-96; http://dx.doi.org/10.1289/ehp.1409557.

Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens

PubMed Central

David, Rhiannon; Ebbels, Timothy; Gooderham, Nigel

2015-01-01

Background Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined. Objectives We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar). Methods Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry. Results Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair. Conclusions Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. Citation David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88–96; http://dx.doi.org/10.1289/ehp.1409557 PMID:26091049

MORPHOLOGICAL CELL TRANSFORMATION OF C3H10T1/2CL8 MOUSE EMBRYO CELLS BY THE K-REGION DIHYDRODIOL OF BENZO[A]PYRENE OCCURS IN COINCIDENCE WITH DNA DAMAGE, BUT WITHOUT THE FORMATION OF DETECTABLE STABLE COVALENT DNA ADDUCTS

EPA Science Inventory

Abstract:

Benzo[a]pyrene (B[a]P) has been the most thoroughly studied polycyclic aromatic hydrocarbon (PAH). Many mechanisms have been suggested to explain its carcinogenic activity, yet many questions still remain. K-region diols of PAHs are common metabolic inter...

THE K-REGION DIHYDRODIOL OF BENZO[A]PYRENE INDUCES DNA DAMAGE AND MORPHOLOGICAL CELL TRANSFORMATION IN C3H10T1/2CL8 MOUSE EMBRYO CELLS WITHOUT THE FORMATION OF DETECTABLE STABLE COVALENT DNA ADDUCTS

EPA Science Inventory

The K -region dihydrodiol ofbenzo[ a ]pyrene induces DNA damage and morphological cell transformation in C3HlOTY2CL8 mouse embryo cells without the formation of detectable stable covalent DNA adducts

Benzo[ a ]pyrene (B[ a ]P) is the most thoroughly studied polycyclic aro...

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on heat processing contaminants.

PubMed

Schütte, Katrin; Boeing, Heiner; Hart, Andy; Heeschen, Walther; Reimerdes, Ernst H; Santare, Dace; Skog, Kerstin; Chiodini, Alessandro

2012-11-01

The aim of the European Funded Project BRAFO (benefit-risk analysis of foods) project was to develop a framework that allows quantitative comparison of human health risks and benefits of foods based on a common scale of measurement. This publication describes the application of the BRAFO methodology to three different case studies: the formation of acrylamide in potato and cereal based products, the formation of benzo(a)pyrene through smoking and grilling of meat and fish and the heat-treatment of milk. Reference, alternative scenario and target population represented the basic structure to test the tiers of the framework. Various intervention methods intended to reduce acrylamide in potato and cereal products were evaluated against the historical production methods. In conclusion the benefits of the acrylamide-reducing measures were considered prevailing. For benzo(a)pyrene, three illustrated alternative scenarios were evaluated against the most common smoking practice. The alternative scenarios were assessed as delivering benefits, introducing only minimal potential risks. Similar considerations were made for heat treatment of milk where the comparison of the microbiological effects of heat treatment, physico-chemical changes of milk constituents with positive and negative health effects was assessed. In general, based on data available, benefits of the heat treatment were outweighing any risks. Copyright © 2012 ILSI Europe. Published by Elsevier Ltd.. All rights reserved.

The selective cleanup of complex matrices and simultaneous separation of benzo[a]pyrene by solid-phase extraction with MgO microspheres as sorbents.

PubMed

Jin, Jing; Li, Yun; Zhang, Zhiping; Su, Fan; Qi, Peipei; Lu, Xianbo; Chen, Jiping

2011-12-23

A new method for the selective cleanup of complex matrices and simultaneous separation of benzo[a]pyrene (BaP) was developed in this study. This method was based on solid-phase extraction (SPE) using magnesium oxide microspheres as sorbents, and it eliminated interferences from various impurities, such as lipids, sulphur, pigments, halobenzenes, polychlorodibenzo-p-dioxins and polychlorodibenzofurans. Several parameters, including the volume of rinsing and eluting solvents, the type of loading solvents and SPE sorbents, were optimized systematically. The capability for impurity removal was verified by gel permeation chromatography, gas chromatography, and liquid chromatography. Compared to commercial sorbents (silica gel, florisil and alumina), MgO microspheres exhibited excellent performance in the selective isolation of BaP and removal of impurities. The proposed method was applied to detect BaP in complex samples (sediments, soils, fish, and porcine liver). The limit of quantification (LOQ) was 1.04 ngL(-1), and the resulting regression coefficient (r(2)) was greater than 0.999 over a broad concentration range (9.5-7600 ngL(-1)). In contrast to traditional methods, the proposed method can give rise to higher recovery (85.1-100.8%) and better selectivity with simpler operation and less consumption of organic solvents (20-40 mL). Copyright © 2011 Elsevier B.V. All rights reserved.

Reproductive toxicity assessment of benzo[a]pyrene in the marine polychaete Perinereis nuntia

NASA Astrophysics Data System (ADS)

Wu, Qingyang; Wang, Shuqi; Chen, Xiaopeng; Li, Ping

2017-07-01

Benzo[a]pyrene (B[a]P) is an increasingly present marine environmental pollutant, yet our understanding of the long-term consequences of reproductive toxicity in marine benthic polychaetes remains limited. To test the reproductive toxicity of B[a]P on polychaetes, Perinereis nuntia was exposed to B[a]P-contaminated artificial seawater and sexual maturation, the sex ratio, number of eggs spawned, fertilization and hatching rated, as well as vitellogenin (VTG) mRNA expression levels were analyzed. A low concentration of B[a]P (2.5 μg/L) had no effects on the rate of sexual maturation, spawning, or fertilization but significantly increased the sex ratio (female: male) from 1.6±0.15:1 to 2.3±0.18:1, inhibited hatching rate by 27%, and significantly increased VTG mRNA expression level by 3.7-fold following a 60-day exposure, compared with those in the solvent controls. A higher concentration of B[a]P (25 μg/L) caused more serious effects; sexual maturation, fertilization success, and hatching decreased by 31%, 17% and 46%, respectively, and the sex ratio (female: male) and VTG mRNA gene expression level increased by 54% and 7.1-fold, respectively. These results demonstrate that sublethal concentrations of B[a]P negatively affect reproductive performance of the sandworm P. nuntia.

Effects of coke oven emissions and benzo[a]pyrene on blood pressure and electrocardiogram in coke oven workers.

PubMed

Yang, Kai; Jiang, Xuejun; Cheng, Shuqun; Chen, Chengzhi; Cao, Xianqing; Tu, Baijie

2017-01-24

To evaluate the effects of occupational exposures to coke oven emissions (COEs) and benzo[a]pyrene (B[a]P) on the prevalence of hypertension and abnormal electrocardiogram (ECG) in coke oven workers. We included 880 coke oven workers and 710 oxygen employees in the exposed and control groups, respectively. Blood pressure (BP), ECG, blood lipid levels, and glucose levels of all subjects were measured. COE and B[a]P concentrations at the bottom, side, and top of the oven and control plants were estimated by weighing and high-performance liquid chromatography. The COE concentration at the top and side was higher than that at the bottom (P < 0.05). The levels of B[a]P at the top and side significantly exceeded the limit value. Abnormal BP, ECG, the detection ratio of hypertension and left ventricular high voltage were significantly greater in the exposed group than in the control group (P < 0.05). The logistic regression analysis results revealed that age and B[a]P exposure were risk factors for hypertension in coke oven workers (P < 0.05) and both were risk factors for abnormal ECG (P < 0.05). Moreover, B[a]P exposure, age, and gender were risk factors for impaired fasting glucose in coke oven workers (P < 0.05). B[a]P and COE exposures are risk factors for hypertension and abnormal ECG in coke oven workers.

Hydroxypropyl cyclic β-(1 → 2)-D-glucans and epichlorohydrin β-cyclodextrin dimers as effective carbohydrate-solubilizers for polycyclic aromatic hydrocarbons.

PubMed

Choi, Jae Min; Jeong, Daham; Piao, Jinglan; Kim, Kyoungtea; Nguyen, Andrew Bao Loc; Kwon, Nak-Jung; Lee, Mi-Kyung; Lee, Im Soon; Yu, Jae-Hyuk; Jung, Seunho

2015-01-12

The removal of polycyclic aromatic hydrocarbons by soil washing using water is extremely difficult due to their intrinsic hydrophobic nature. In this study, the effective aqueous solubility enhancements of seven polycyclic aromatic hydrocarbons by chemically modified hydroxypropyl rhizobial cyclic β-(1 → 2)-D-glucans and epichlorohydrin β-cyclodextrin dimer have been investigated for the first time. In the presence of hydroxypropyl cyclic β-(1 → 2)-D-glucans, the solubility of benzo[a]pyrene is increased up to 38 fold of its native solubility. The solubility of pyrene and phenanthrene dramatically increased up to 160 and 359. Coronene, chrysene, perylene, and fluoranthene also show an increase of 11, 23, 23, and 97 fold, respectively, of enhanced solubility by complexation with synthetic epichlorohydrin β-cyclodextrin dimer. The physicochemical properties of the complex are characterized by Fourier-transform infrared spectra and differential scanning calorimetry. Utilizing a scanning electron microscopy, the morphological structures of native benzo[a]pyrene, pyrene, phenanthrene, coronene, chrysene, perylene, fluoranthene and their complex with novel carbohydrate-solubilizers are studied. These results elucidate that polycyclic aromatic hydrocarbons are able to form an efficient complex with hydroxypropyl cyclic β-(1 → 2)-D-glucans and β-cyclodextrin dimer, suggesting the potential usage of chemically modified novel carbohydrate-solubilizers. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of antigenotoxic effects of carotenoids from green algae Chlorococcum humicola using human lymphocytes

PubMed Central

Bhagavathy, S; Sumathi, P

2012-01-01

Objective To identify the available phytochemicals and carotenoids in the selected green algae and evaluate the potential genotoxic/antigenotoxic effect using lymphocytes. Methods Organic solvent extracts of Chlorococcum humicola (C. humicola) were used for the phytochemical analysis. The available carotenoids were assessed by HPLC, and LC-MS analysis. The genotoxicity was induced by the benzo(a)pyrene in the lymphocyte culture, the genotoxic and antigenotoxic effects of algal carotenoids with and without genotoxic inducer were evaluated by chromosomal aberration (CA), sister chromatid exchange (SCE) and micronucleus assay (MN). Results The results of the analysis showed that the algae were rich in carotenoids and fatty acids. In the total carotenoids lutein, β-carotene and α-carotene were found to be present in higher concentration. The frequency of CA and SCE increased by benzo(a)pyrene were significantly decreased by the carotenoids (P<0.05 for CA, P<0.001 for SCE). The MN frequencies of the cells were significantly decreased by the treatment with carotenoids when compared with the positive controls (P<0.05). Conclusions The findings of the present study demonstrate that, the green algae C. humicola is a rich source of bioactive compounds especially carotenoids which effectively fight against environmental genotoxic agents, the carotenoids itself is not a genotoxic substance and should be further considered for its beneficial effects. PMID:23569879

Cancer risk assessment of polycyclic aromatic hydrocarbon contaminated soils determined using bioassay-derived levels of benzo[a]pyrene equivalents.

PubMed

Lemieux, Christine L; Long, Alexandra S; Lambert, Iain B; Lundstedt, Staffan; Tysklind, Mats; White, Paul A

2015-02-03

Here we evaluate the excess lifetime cancer risk (ELCR) posed by 10 PAH-contaminated soils using (i) the currently advocated, targeted chemical-specific approach that assumes dose additivity for carcinogenic PAHs and (ii) a bioassay-based approach that employs the in vitro mutagenic activity of the soil fractions to determine levels of benzo[a]pyrene equivalents and, by extension, ELCR. Mutagenic activity results are presented in our companion paper.1 The results show that ELCR values for the PAH-containing fractions, determined using the chemical-specific approach, are generally (i.e., 8 out of 10) greater than those calculated using the bioassay-based approach; most are less than 5-fold greater. Only two chemical-specific ELCR estimates are less than their corresponding bioassay-derived values; differences are less than 10%. The bioassay-based approach, which permits estimation of ELCR without a priori knowledge of mixture composition, proved to be a useful tool to evaluate the chemical-specific approach. The results suggest that ELCR estimates for complex PAH mixtures determined using a targeted, chemical-specific approach are reasonable, albeit conservative. Calculated risk estimates still depend on contentious PEFs and cancer slope factors. Follow-up in vivo mutagenicity assessments will be required to validate the results and their relevance for human health risk assessment of PAH-contaminated soils.

Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

PubMed

MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

1991-01-01

The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

Alterations in benzo(A)pyrene metabolism and in vivo binding to hepatic DNA in rats red diets containing menhaden oil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wade, A.E.; Dharwadkar, S.

1987-01-01

Polyunsaturated fatty acids of the omega-6 type have been shown to support the mixed function oxidases (MFO) responsible for carcinogen activation and to promote tumorigenesis in laboratory animals. The omega-3 fatty acids contained in menhaden oil (MO) have been shown to enhance MFO activity and increase the binding of Benzo(a)pyrene (B(a)P) metabolites to calf thymus DNA in an in vitro microsomal system. Rats fed two levels of MO (0.5% and 20%) for 11 days received a single i.p. dose of (/sup 3/H)B(a)P (5 m Ci/kg) dissolved in DMSO. At selected time intervals thereafter rats were killed, blood withdrawn, livers removedmore » and DNA extracted. Hepatic microsomes were recovered from control rats on each diet at the time of B(a)P administration to assess MFO activities. Binding of B(a)P to DNA was higher in rats fed the 20% MO diet suggesting an increased rate of B(a)P activation. Blood levels of B(a)P were elevated at 16 and 24 hours post B(a)P, however no differences in urine concentrations were observed. Elevations in concentration of cytochrome P-450, ethoxycoumarin dealkylase, and glutathione S-transferase suggest that omega-3 fatty acids of menhaden fish oil support MFO related reactions not unlike the omega-6 fatty acids.« less

Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital.

PubMed

Schraplau, Anne; Schewe, Bettina; Neuschäfer-Rube, Frank; Ringel, Sebastian; Neuber, Corinna; Kleuser, Burkhard; Püschel, Gerhard P

2015-02-03

Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. Copyright © 2014. Published by Elsevier Ireland Ltd.

Comparative Evaluation of Different Cell Lysis and Extraction Methods for Studying Benzo(a)pyrene Metabolism in HT-29 Colon Cancer Cell Cultures

PubMed Central

Myers, Jeremy N.; Rekhadevi, Perumalla V.; Ramesh, Aramandla

2011-01-01

Lysis and extraction of cells are essential sample processing steps for investigations pertaining to metabolism of xenobiotics in cell culture studies. Of particular importance to these procedures are maintaining high lysis efficiency and analyte integrity as they influence the qualitative and quantitative distribution of drug and toxicant metabolites in the intra- and extracellular milieus. In this study we have compared the efficiency of different procedures viz. homogenization, sonication, bead beating, and molecular grinding resin treatment for disruption of HT-29 colon cells exposed to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound and a suspected colon carcinogen. Also, we have evaluated the efficiency of various procedures for extracting BaP parent compound/metabolites from colon cells and culture media prior to High Performance Liquid Chromatography (HPLC) analyses. The extraction procedures include solid phase extraction, solid-supported liquid- liquid extraction, liquid-liquid extraction, and homogeneous liquid- liquid extraction. Our findings showed that bead-beating in combination with detergent treatment of cell pellet coupled with liquid-liquid extraction yielded greater concentrations of BaP metabolites compared to the other methods employed. Our method optimization strategy revealed that disruption of HT-29 colon cells by a combination of mechanical and chemical lysis followed by liquid-liquid extraction is efficient and robust enough for analyzing BaP metabolites from cell culture studies. PMID:21865728

Crude cacao Theobroma cacao extract reduces mutagenicity induced by benzo[a]pyrene through inhibition of CYP1A activity in vitro.

PubMed

Ohno, Marumi; Sakamoto, Kentaro Q; Ishizuka, Mayumi; Fujita, Shoichi

2009-08-01

Polyphenols have been shown to have potent antioxidant activity, and therefore, food containing polyphenols is expected to contribute to the prevention of cancer. However, food contains not only polyphenols but also various other constituents. We used the Ames test to investigate the effects of crude extracts of whole cacao products, which are known to be rich in polyphenols, on the mutagenicity of benzo[a]pyrene (B[a]P) in Salmonella typhimurium strain TA 98 and tert-butyl hydroperoxide (t-BuOOH) in S. typhimurium strain TA 102. B[a]P induces mutagenicity by metabolic activation and t-BuOOH induces it by generation of free radicals. While white chocolate did not modulate the numbers of revertant colonies produced by B[a]P treatment, milk chocolate and cacao powder extracts did. On the other hand, surprisingly, none of the cacao products tested affected the number of revertant colonies when t-BuOOH was used as the mutagen. At maximum concentration (13.25 mg cacao powder/ml), the crude cacao powder extract reduced ethoxyresorufin O-deethylase activity to 17.4% of the control, suggesting that whole cacao products inhibit cytochrome P450 (CYP) 1A activity. In conclusion, inhibition of CYP1A activity by cacao products may prevent DNA damage by reducing metabolic activation of carcinogens. Copyright 2009 John Wiley & Sons, Ltd.

Beneficial contribution of the arbuscular mycorrhizal fungus, Rhizophagus irregularis, in the protection of Medicago truncatula roots against benzo[a]pyrene toxicity.

PubMed

Lenoir, Ingrid; Fontaine, Joël; Tisserant, Benoît; Laruelle, Frédéric; Lounès-Hadj Sahraoui, Anissa

2017-07-01

Arbuscular mycorrhizal fungi are able to improve plant establishment in polluted soils but little is known about the genes involved in the plant protection against pollutant toxicity by mycorrhization, in particular in the presence of polycyclic aromatic hydrocarbons (PAH). The present work aims at studying in both symbiotic partners, Medicago truncatula and Rhizophagus irregularis: (i) expression of genes putatively involved in PAH tolerance (MtSOD, MtPOX, MtAPX, MtGST, MtTFIIS, and MtTdp1α), (ii) activities of antioxidant (SOD, POX) and detoxification (GST) enzymes, and (iii) H 2 O 2 and the heavy PAH, benzo[a]pyrene (B[a]P) accumulation. In the presence of B[a]P, whereas induction of the enzymatic activities was detected in R. irregularis and non-mycorrhizal roots as well as upregulation of the gene expressions in the non-mycorrhizal roots, downregulation of the gene expressions and decrease of enzyme activities were observed in mycorrhizal roots. Moreover, B[a]P increased H 2 O 2 production in non-mycorrhizal roots and in R. irregularis but not in mycorrhizal roots. In addition, a lower B[a]P bioaccumulation in mycorrhizal roots was measured in comparison with non-mycorrhizal roots. Being less affected by pollutant toxicity, mycorrhizal roots did not activate any defense mechanism either at the gene expression regulation level or at the enzymatic level.

Metabolically Competent Human Skin Models: Activation and Genotoxicity of Benzo[a]pyrene

PubMed Central

Henkler, Frank

2013-01-01

The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BP) is metabolized into a complex pattern of BP derivatives, among which the ultimate carcinogen (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE) is formed to certain extents. Skin is frequently in contact with PAHs and data on the metabolic capacity of skin tissue toward these compounds are inconclusive. We compared BP metabolism in excised human skin, commercially available in vitro 3D skin models and primary 2D skin cell cultures, and analyzed the metabolically catalyzed occurrence of seven different BP follow-up products by means of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). All models investigated were competent to metabolize BP, and the metabolic profiles generated by ex vivo human skin and skin models were remarkably similar. Furthermore, the genotoxicity of BP and its derivatives was monitored in these models via comet assays. In a full-thickness skin, equivalent BP-mediated genotoxic stress was generated via keratinocytes. Cultured primary keratinocytes revealed a level of genotoxicity comparable with that of direct exposure to 50–100nM of BPDE. Our data demonstrate that the metabolic capacity of human skin ex vivo, as well as organotypic human 3D skin models toward BP, is sufficient to cause significant genotoxic stress and thus cutaneous bioactivation may potentially contribute to mutations that ultimately lead to skin cancer. PMID:23148024

The environmental carcinogen benzo[a]pyrene induces a Warburg-like metabolic reprogramming dependent on NHE1 and associated with cell survival

PubMed Central

Hardonnière, Kévin; Saunier, Elise; Lemarié, Anthony; Fernier, Morgane; Gallais, Isabelle; Héliès-Toussaint, Cécile; Mograbi, Baharia; Antonio, Samantha; Bénit, Paule; Rustin, Pierre; Janin, Maxime; Habarou, Florence; Ottolenghi, Chris; Lavault, Marie-Thérèse; Benelli, Chantal; Sergent, Odile; Huc, Laurence; Bortoli, Sylvie; Lagadic-Gossmann, Dominique

2016-01-01

Cancer cells display alterations in many cellular processes. One core hallmark of cancer is the Warburg effect which is a glycolytic reprogramming that allows cells to survive and proliferate. Although the contributions of environmental contaminants to cancer development are widely accepted, the underlying mechanisms have to be clarified. Benzo[a]pyrene (B[a]P), the prototype of polycyclic aromatic hydrocarbons, exhibits genotoxic and carcinogenic effects, and it is a human carcinogen according to the International Agency for Research on Cancer. In addition to triggering apoptotic signals, B[a]P may induce survival signals, both of which are likely to be involved in cancer promotion. We previously suggested that B[a]P-induced mitochondrial dysfunctions, especially membrane hyperpolarization, might trigger cell survival signaling in rat hepatic epithelial F258 cells. Here, we further characterized these dysfunctions by focusing on energy metabolism. We found that B[a]P promoted a metabolic reprogramming. Cell respiration decreased and lactate production increased. These changes were associated with alterations in the tricarboxylic acid cycle which likely involve a dysfunction of the mitochondrial complex II. The glycolytic shift relied on activation of the Na+/H+ exchanger 1 (NHE1) and appeared to be a key feature in B[a]P-induced cell survival related to changes in cell phenotype (epithelial-to-mesenchymal transition and cell migration). PMID:27488617

Toxic responses of Perna viridis hepatopancreas exposed to DDT, benzo(a)pyrene and their mixture uncovered by iTRAQ-based proteomics and NMR-based metabolomics.

PubMed

Song, Qinqin; Zhou, Hailong; Han, Qian; Diao, Xiaoping

2017-11-01

Dichlorodiphenyltrichloroethane (DDT) and benzo(a)pyrene (BaP) are environmental estrogens (EEs) that are ubiquitous in the marine environment. In the present study, we integrated isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic and nuclear magnetic resonance (NMR)-based metabolomic approaches to explore the toxic responses of green mussel hepatopancreas exposed to DDT (10μg/L), BaP (10μg/L) and their mixture. The metabolic responses indicated that BaP primarily disturbed energy metabolism and osmotic regulation in the hepatopancreas of the male green mussel P. viridis. Both DDT and the mixture of DDT and BaP perturbed the energy metabolism and osmotic regulation in P. viridis. The proteomic responses revealed that BaP affected the proteins involved in energy metabolism, material transformation, cytoskeleton, stress responses, reproduction and development in green mussels. DDT exposure could change the proteins involved in primary metabolism, stress responses, cytoskeleton and signal transduction. However, the mixture of DDT and BaP altered proteins associated with material and energy metabolism, stress responses, signal transduction, reproduction and development, cytoskeleton and apoptosis. This study showed that iTRAQ-based proteomic and NMR-based metabolomic approaches could effectively elucidate the essential molecular mechanism of disturbances in hepatopancreas function of green mussels exposed to environmental estrogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Long-term exposure to urban air pollution and the relationship with life expectancy in cohort of 3.5 million people in Silesia.

PubMed

Dziubanek, Grzegorz; Spychała, Anna; Marchwińska-Wyrwał, Ewa; Rusin, Monika; Hajok, Ilona; Ćwieląg-Drabek, Małgorzata; Piekut, Agata

2017-02-15

Air pollution is considered to be one of the most important environmental health determinants. The studies constitute an attempt to explain the role of air pollutants in the impact on the length of life of the 3.5 million people living in the cities of the Silesia province in Poland. The association between the long-term inhalation exposure to PM 10 , benzo(a)pyrene, cadmium and lead in the period from 1989 to 2008 and length of life in the year 2014 of the inhabitants of 19 cities of the Silesia province has been estimated. The Pearson linear regression method was applied to calculate the relation between exposure to specific pollutants and length of life. In order to determine the influence of the mixture of the pollutants the multiple regression analysis was carried out. The studies have confirmed the significant correlations between the chronic exposure of Silesia province residents to PM 10 and benzo(a)pyrene and their length of life. The stronger correlation was demonstrated in case of the long-term exposure to the mixture of examined air pollutants. Differentiated exposure of the inhabitants of the Silesia province to air pollutants results in existing inequalities in the life expectancy of men and women among the cities. Copyright © 2016 Elsevier B.V. All rights reserved.

Benzene, benzo(a)pyrene, and lead in smoke from tobacco products other than cigarettes.

PubMed Central

Appel, B R; Guirguis, G; Kim, I S; Garbin, O; Fracchia, M; Flessel, C P; Kizer, K W; Book, S A; Warriner, T E

1990-01-01

Benzene, benzo(a)pyrene (BaP), and lead in mainstream smoke from cigars, roll-your-own (RYO) cigarette and pipe tobaccos were sampled to evaluate their potential health significance. Results with reference cigarettes were consistent with published values, providing support for the methodology employed. The emissions of benzene and BaP, expressed as mass emitted per gram of tobacco consumed, were similar for all products evaluated; for benzene, the mean values for cigars, RYO cigarette and pipe tobaccos were 156 +/- 52, 68 +/- 11, and 242 +/- 126 micrograms/g, respectively. Mean values for BaP were 42 +/- 7 and 48 +/- 4 ng/g for cigars and RYO cigarette tobacco, respectively. Lead values were below the limit of reliable quantitation in all cases. The mean benzene concentrations in a puff ranged from 1 to 2 x 10(5) micrograms/m3 for cigars, RYO cigarette and pipe tobaccos. For BaP, the puff concentration averaged about 60 micrograms/m3 for cigars and RYO cigarette tobacco. The results suggest that smoking cigars, pipes or RYO cigarettes leads to potential exposures which exceed the No Significant Risk levels of benzene and BaP set pursuant to California's Proposition 65. These tobacco products are now required to bear a health hazard warning when sold in California. We recommend that this be adopted as national policy. PMID:2327532

Benzo[a]pyrene, Aflatoxine B1 and Acetaldehyde Mutational Patterns in TP53 Gene Using a Functional Assay: Relevance to Human Cancer Aetiology

PubMed Central

Paget, Vincent; Lechevrel, Mathilde; André, Véronique; Le Goff, Jérémie; Pottier, Didier; Billet, Sylvain; Garçon, Guillaume; Shirali, Pirouz; Sichel, François

2012-01-01

Mutations in the TP53 gene are the most common alterations in human tumours. TP53 mutational patterns have sometimes been linked to carcinogen exposure. In hepatocellular carcinoma, a specific G>T transversion on codon 249 is classically described as a fingerprint of aflatoxin B1 exposure. Likewise G>T transversions in codons 157 and 158 have been related to tobacco exposure in human lung cancers. However, controversies remain about the interpretation of TP53 mutational pattern in tumours as the fingerprint of genotoxin exposure. By using a functional assay, the Functional Analysis of Separated Alleles in Yeast (FASAY), the present study depicts the mutational pattern of TP53 in normal human fibroblasts after in vitro exposure to well-known carcinogens: benzo[a]pyrene, aflatoxin B1 and acetaldehyde. These in vitro patterns of mutations were then compared to those found in human tumours by using the IARC database of TP53 mutations. The results show that the TP53 mutational patterns found in human tumours can be only partly ascribed to genotoxin exposure. A complex interplay between the functional impact of the mutations on p53 phenotype and the cancer natural history may affect these patterns. However, our results strongly support that genotoxins exposure plays a major role in the aetiology of the considered cancers. PMID:22319594

Development of a Toolbox Using Chemical, Physical and Biological Technologies for Decontamination of Sediments to Support Strategic Army Response to Natural Disasters

DTIC Science & Technology

2006-11-01

disinfection) was tested using soil microcosms and respirometry to determine diesel range and total organic compound degradation. These tests were...grease) such as benzo(a)pyrene were detected above chronic (long term-measured in years) screening levels. Levels of diesel and oil range organics... bioremediation , and toxicity of liquid and solid samples. The Comput-OX 4R is a 4 reactor unit with no stirring modules or temperature controlled water bath

A Comparative Study of the Metabolism of 6-Methylbenzo [A] Pyrene and Benzo [A] Pyrene by Rat Liver Microsomes

DTIC Science & Technology

1984-02-24

147. Dewhurst, F., and Kitchen, D. A. (1972). Synthesis and properties of 6-substituted benzo [a] pyrene derivatives. J_. £. 1 . Perkins I, 710-712...group results in the formation of 6-hydroxymathylbenzo[a]pyrene (6-OHMBaP) which can be further metabolized to both the 1 - and 3-phenols of 6...LIST OF TABLES LIST OF FIGURES xi BACKGROUND 1 Introduction 1 Metabolism of PAH 1 Microsomal Metabolism of Benzo[a]pyrene 2 Inducers of

Accelerated removal of pyrene and benzo[a]pyrene in freshwater sediments with amendment of cyanobacteria-derived organic matter.

PubMed

Yan, Zaisheng; Jiang, Helong; Li, Xiaohong; Shi, Yuan

2014-05-15

The removal of pyrene and benzo[a]pyrene (BaP) were investigated in freshwater sediments with amendment of seven different organic matters including cyanobacteria-derived organic matter (COM), plant-derived organic matter (POM), and humic substances (HS). During the 210 days of experiments, the amendment of COM or HS enhanced significantly the removal of pyrene and BaP in sediments, especially with fresh COM (FCOM) treatment much superior to HS. On the contrary, degradation of these polycyclic aromatic hydrocarbons (PAHs) was not significantly improved and even inhibited in POM-amended sediments. The first-order rate constants of pyrene and BaP degradation in the FCOM-amended sediments reached 0.00540±0.00017d(-1) and 0.00517±0.00057d(-1), respectively, and were about three and five folds of those in the control treatment. The enhanced PAHs degradation in FCOM-amended sediments was related to higher PAH-degrading bacteria number and bioavailability with a result of biostimulation and priming effect by labile carbon and high-value nutrition in FCOM. Thus, this study improved our understanding about effects of settled biomass from cyanobacterial blooms, which occurred frequently in eutrophic aquatic ecosystems, on the natural attenuation of PAHs in sediments. Furthermore, this study would also help develop a new promising approach to remediate PAH-contaminated sediments through utilization of cyanobacterial bloom biomass. Copyright © 2014 Elsevier B.V. All rights reserved.

Estimating exposures in the asphalt industry for an international epidemiological cohort study of cancer risk.

PubMed

Burstyn, Igor; Boffetta, Paolo; Kauppinen, Timo; Heikkilä, Pirjo; Svane, Ole; Partanen, Timo; Stücker, Isabelle; Frentzel-Beyme, Rainer; Ahrens, Wolfgang; Merzenich, Hiltrud; Heederik, Dick; Hooiveld, Mariëtte; Langård, Sverre; Randem, Britt G; Järvholm, Bengt; Bergdahl, Ingvar; Shaham, Judith; Ribak, Joseph; Kromhout, Hans

2003-01-01

An exposure matrix (EM) for known and suspected carcinogens was required for a multicenter international cohort study of cancer risk and bitumen among asphalt workers. Production characteristics in companies enrolled in the study were ascertained through use of a company questionnaire (CQ). Exposures to coal tar, bitumen fume, organic vapor, polycyclic aromatic hydrocarbons, diesel fume, silica, and asbestos were assessed semi-quantitatively using information from CQs, expert judgment, and statistical models. Exposures of road paving workers to bitumen fume, organic vapor, and benzo(a)pyrene were estimated quantitatively by applying regression models, based on monitoring data, to exposure scenarios identified by the CQs. Exposures estimates were derived for 217 companies enrolled in the cohort, plus the Swedish asphalt paving industry in general. Most companies were engaged in road paving and asphalt mixing, but some also participated in general construction and roofing. Coal tar use was most common in Denmark and The Netherlands, but the practice is now obsolete. Quantitative estimates of exposure to bitumen fume, organic vapor, and benzo(a)pyrene for pavers, and semi-quantitative estimates of exposure to these agents among all subjects were strongly correlated. Semi-quantitative estimates of exposure to bitumen fume and coal tar exposures were only moderately correlated. EM assessed non-monotonic historical decrease in exposures to all agents assessed except silica and diesel exhaust. We produced a data-driven EM using methodology that can be adapted for other multicenter studies. Copyright 2003 Wiley-Liss, Inc.

Impacts of UV radiation and photomodification on the toxicity of PAHs to the higher plant Lemna gibba (duckweed)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiaodong Huang; Dixon, D.G.; Greenberg, B.M.

1993-06-01

The toxicity of polycyclic aromatic hydrocarbons (PAHs) can be enhanced by both biotic and abiotic processes. This is exemplified by light, which, by virtue of the extensive [pi]-orbital systems of PAHs, can be a major factor in PAH toxicity. Light activation of PAHs is known to occur via photosensitization reactions and potentially by photomodification of the chemicals to more toxic species. To examine the modes of PAH action in the light and determine if the photomodified compounds are hazardous, the authors investigated the photoinduced toxicity of anthracene, phenanthrene and benzo[a]pyrene to the aquatic higher plant Lemna gibba (a duckweed). Toxicitymore » end points were inhibition of growth and extent of chlorosis. Light did indeed activated the phytotoxicity of PAHs, with UV radiation more effective than visible light. Dose-response curves based on chemical concentration and light intensity revealed the order of phytotoxic strength to be anthracene > phenanthrene > benzo[a]pyrene. To explore whether photomodified PAHs were contributing to toxicity, the chemicals were irradiated before toxicity testing. The rates of photomodification of the three PAHs were rapid, and the relative velocities were coincident with the order of toxic strength. Furthermore, the photomodified PAHs were more hazardous to Lemna than the intact compounds. Because interpretations of the potential impacts of PAHs in the environment are based mostly on measurements of the structurally intact chemicals, the severity of PAH hazards is possibly underestimated.« less

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation

PubMed Central

2011-01-01

Background Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. Methods During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Results Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. Conclusions The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace. PMID:21435260

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation.

PubMed

Al Zabadi, Hamzeh; Ferrari, Luc; Sari-Minodier, Irène; Kerautret, Marie-Aude; Tiberguent, Aziz; Paris, Christophe; Zmirou-Navier, Denis

2011-03-24

Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace.

Combined field/modelling approaches to represent the air-vegetation distribution of benzo[a]pyrene using different vegetation species

NASA Astrophysics Data System (ADS)

Ratola, Nuno; Jiménez-Guerrero, Pedro

2015-04-01

A strategy designed to combine the features of field-based experiments and modelling approaches is presented in this work to assess air-vegetation distribution of benzo(a)pyrene (BaP) in the Iberian Peninsula (IP). Given the lack of simultaneous data in both environmental matrices, a methodology with two main steps was employed. First, evaluating the simulations with the chemistry transport model (CTM) WRF (Weather Research and Forecasting) + CHIMERE data against the European Monitoring and Evaluation Programme (EMEP) network, to test the aptitude of the CTM to replicate the respective atmospheric levels. Then, using modelled concentrations and a method to estimate air levels of BaP from biomonitoring data to compare the performance of different pine species (Pinus pinea, Pinus pinaster, Pinus nigra and Pinus halepensis) to describe the atmospheric evidences. The comparison of modelling vs. biomonitoring has a higher dependence on the location of the sampling points, rather than on the pine species, as some tend to overestimate and others to underestimate BaP concentrations, in most cases regardless of the season. The climatology of the canopy levels of BaP was successfully validated with the concentrations in pine needles (most biases below 26%), however, the model was unable to distinguish between species. This should be taken into consideration in future studies, as biases can rise up to 48%, especially in summer and autumn, the. The comparison with biomonitoring data showed a similar pattern, but with the best results in the warmer months.

Effects of coke oven emissions and benzo[a]pyrene on blood pressure and electrocardiogram in coke oven workers

PubMed Central

Yang, Kai; Jiang, Xuejun; Cheng, Shuqun; Chen, Chengzhi; Cao, Xianqing; Tu, Baijie

2016-01-01

Objective: To evaluate the effects of occupational exposures to coke oven emissions (COEs) and benzo[a]pyrene (B[a]P) on the prevalence of hypertension and abnormal electrocardiogram (ECG) in coke oven workers. Methods: We included 880 coke oven workers and 710 oxygen employees in the exposed and control groups, respectively. Blood pressure (BP), ECG, blood lipid levels, and glucose levels of all subjects were measured. COE and B[a]P concentrations at the bottom, side, and top of the oven and control plants were estimated by weighing and high-performance liquid chromatography. Results: The COE concentration at the top and side was higher than that at the bottom (P < 0.05). The levels of B[a]P at the top and side significantly exceeded the limit value. Abnormal BP, ECG, the detection ratio of hypertension and left ventricular high voltage were significantly greater in the exposed group than in the control group (P < 0.05). The logistic regression analysis results revealed that age and B[a]P exposure were risk factors for hypertension in coke oven workers (P < 0.05) and both were risk factors for abnormal ECG (P < 0.05). Moreover, B[a]P exposure, age, and gender were risk factors for impaired fasting glucose in coke oven workers (P < 0.05). Conclusions: B[a]P and COE exposures are risk factors for hypertension and abnormal ECG in coke oven workers. PMID:27885241

Effects of quantity, quality, and contact time of dissolved organic matter on bioconcentration of benzo[a]pyrene in the nematode Caenorhabditis elegans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haitzer, M.; Hoess, S.; Burnison, B.K.

1999-03-01

Quantity and quality of dissolved organic matter (DOM) and the time allowed for DOM to interact with organic contaminants can influence their bioavailability. The authors studied the effect of natural aquatic DOM that had been in contact with benzo[a]pyrene (B[a]P) for 1 to 12 d on the bioconcentration of B[a]P in the nematode Caenorhabditis elegans. Dissolved organic matter quality and quantity was varied by using DOM from three different sources, each in three different concentrations. A model, based on the assumption that only freely dissolved B[a]P is bioavailable, was employed to estimate biologically determined partition coefficients [K{sub p}(biol.)]. Expressing themore » data for each combination of DOM source and contact time in a single K{sub p} (biol.) value allowed a direct comparison of the effects of different DOM qualities and contact times. The results show that the effect of DOM from a specific source was dependent on DOM quantity, but they also observed a distinct effect of DOM quality (represented by different sampling locations) on the bioconcentration of B[a]P. Contact time had no significant influence for the effects of two DOM sources on the bioconcentration of B[a]P. However, the third DOM source was significantly more effective with increased contact time, leading to lower B[a]P bioconcentration in the nematodes.« less

UPLC-MS/MS method for the determination of tobacco-specific biomarker NNAL, tamoxifen and its main metabolites in rat plasma.

PubMed

Xiong, Wei; Zhao, Jiajia; Wang, Ling; Jiang, Xuehua

2017-06-01

Cigarette smoke is known to interact with tamoxifen-metabolizing enzymes and transporters and potentially affect its treatment outcome. 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL) is an important metabolite of 4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK) because it is frequently used as a biomarker to assess human smoke exposure. In order to study the potential pharmacokinetic interaction between cigarette smoke and tamoxifen in rats a UPLC-MS/MS method for the simultaneous determination of NNAL and tamoxifen along with its metabolites in rat plasma has been developed and validated. Analytes were extracted with methanol and separated on a HSS T3 column by a gradient elution with the mobile phase consisting of acetonitrile and water. The lower limits of quantitation ranged from 0.05 to 0.62 ng/mL. Precisions showed RSD <15.8% and accuracy in the range 80.6-116.0%. Mean analyte recoveries ranged from 76.9 to 108.4%. The method was successfully applied to study the effects of cigarette smoke condensate (CSC), NNK and benzo(a)pyrene pre-treatment on the pharmacokinetics of tamoxifen and its metabolites in rats. Significant effects of CSC, NNK, benzo(a)pyrene were observed on pharmacokinetics of tamoxifen and its metabolites. We also found that plasma NNAL levels are statistically significant correlated with plasma 4-hydroxy-tamoxifen and endoxifen. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy of PLGA-loaded apigenin nanoparticles in Benzo[a]pyrene and ultraviolet-B induced skin cancer of mice: mitochondria mediated apoptotic signalling cascades.

PubMed

Das, Sreemanti; Das, Jayeeta; Samadder, Asmita; Paul, Avijit; Khuda-Bukhsh, Anisur Rahman

2013-12-01

Skin cancer is increasing at an alarming rate and becoming resistant to conventional chemotherapy necessitating improved drug delivery system. We loaded apigenin (Ap), a dietary flavonoid having anti-cancer property, with poly (lactic-co-glycolide) (PLGA) nanoparticles (NAp) to explore if nano-encapsulation could enhance anti-carcinogenic effect against ultra-violet B (UVB) and Benzo(a)pyrene (BaP) induced skin tumor and mitochondrial dysfunction in mice. Particle size, morphology and zeta potential of NAp were determined using dynamic light scattering and atomic force microscopy. Tumor incidence and multiplicity in UVB-BaP induced mice with/without NAp treatment were ascertained and their histolopathological sections and chromosomal aberrations were studied. ROS accumulation and mitochondrial functioning through relevant markers like mitochondrial transmembrane potential were analyzed. Mitochondrial volume changes/swelling, cytochrome c (cyt c) release, mRNA and protein expressions of Apaf-1, bax, bcl-2, cyt c, cleaved caspase-9 and 3 were studied. Results showed that NAp produced better effects than Ap, due to their smaller size, and faster mobility. NAp reduced tissue damage and frequency of chromosomal aberrations, increased ROS accumulation to mediate mitochondrial-apoptosis through modulation of several apoptotic markers and mitochondrial matrix swelling. NAp showed ameliorative potentials in combating skin cancer and therefore has greater prospect of use in therapeutic management of skin cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of benzo[a]pyrene on detoxification and the activity of antioxidant enzymes of marine microalgae

NASA Astrophysics Data System (ADS)

Shen, Chen; Miao, Jingjing; Li, Yun; Pan, Luqing

2016-04-01

The objective of this study was to examine the effect of benzo[a]pyrene (BaP) on the detoxification and antioxidant systems of two microalgae, Isochrysis zhanjiangensis and Platymonas subcordiformis. In our study, these two algae were exposed to BaP for 4 days at three different concentrations including 0.5 μg L-1 (low), 3 μg L-1 (mid) and 18 μg L-1 (high). The activity of detoxification enzymes, ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) increased in P. subcordiformis in all BaP-treated groups. In I. zhanjiangensis, the activity of these two enzymes increased at the beginning of exposure, and then decreased in the groups treated with mid- and high BaP. The activity of antioxidant enzyme superoxide dismutase (SOD) increased in I. zhanjiangensis in all BaP-treated groups, and then decreased in high BaP-treated group, while no significant change was observed in P. subcordiformis. The activity of antioxidant enzyme catalase (CAT) increased in I. zhanjiangensis and P. subcordiformis in all BaPtreated groups. The content of malondialdehyde (MDA) in Isochrysis zhanjiangensis increased first, and then decreased in high BaP-treated group, while no change occurred in P. subcordiformis. These results demonstrated that BaP significantly influenced the activity of detoxifying and antioxidant enzymes in microalgae. The metabolic related enzymes (EROD, GST and CAT) may serve as sensitive biomarkers of measuring the contamination level of BaP in marine water.

MicroRNA Responses to the Genotoxic Carcinogens Aflatoxin B1 and Benzo[a]pyrene in Human HepaRG Cells.

PubMed

Marrone, April K; Tryndyak, Volodymyr; Beland, Frederick A; Pogribny, Igor P

2016-02-01

Recent advances in toxicogenomics present an opportunity to develop new in vitro testing methodologies to identify human carcinogens. We have investigated microRNA expression responses to the treatment of human liver HepaRG cells with the human genotoxic carcinogens aflatoxin B1 (AFB1) and benzo[a]pyrene (B[a]P), and the structurally similar compounds aflatoxin B2 (AFB2) and benzo[e]pyrene (B[e]P) that exhibit minimal carcinogenic potential. We demonstrate that treatment of HepaRG cells with AFB1 or B[a]P resulted in specific changes in the expression of miRNAs as compared with their non-carcinogenic analogues, particularly in a marked over-expression of miR-410. An additional novel finding is the dose- and time-dependent inhibition of miR-122 in AFB1-treated HepaRG cells. Mechanistically, the AFB1-induced down-regulation of miR-122 was attributed to inhibition of the HNF4A/miR-122 regulatory pathway. These results demonstrate that HepaRG cells can be used to investigate miRNA responses to xenobiotic exposure, and illustrate the existence of early non-genotoxic events, in addition to a well-established genotoxic mode of action changes, in the mechanism of AFB1 and B[a]P carcinogenicity. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

Interaction of Benzo(a)pyrene with the natural organic matter of soil using three-dimensional (3-D) fluorescence spectroscopy with Parallel Factor Analysis

NASA Astrophysics Data System (ADS)

El Fallah, Rawa

2017-04-01

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon arising mainly from the incomplete combustion of organic material. It is toxic and has mutagenic and carcinogenic properties. It is classified as a priority pollutant by The United States Environmental Protection Agency (US-EPA). After it's emission in the atmosphere, and due to its physico-chemical properties, BaP will be deposited in the soil. Its aromaticity gives it the capacity to be studied by fluorescence spectroscopy so that of the Natural Organic Matter (NOM). In this study we used fluorescence excitation-emission-matrix (FEEM) with Parallel Factor analysis (PARAFAC) to study the interaction between NOM of soil and BaP. Soil sample was treated with Tetrasodium pyrophosphate along with Sodium hydroxide to obtain the Humic Substances, which afterwards were physically fractioned under acidic pH into solid Humic Acid and liquid Fulvic Acid. Three concentrations of BaP solution were added to each soil fraction. We compared the results of PARAFAC analysis of the samples containing BaP and the original NOM fractions. In the samples containing BaP, four fluorophores (components) were found, the fourth identified as BaP. Out of the three other fluorophores characteristic of NOM, two were found similar in all NOM fractions whereas only one fluorophore had some variations in its spectral characteristics. The presence of BaP changed the fluorescence of NOM. These modifications were depending on the type of soil fraction.

Effects of Benzo(a)pyrene on Intra-testicular Function in F-344 Rats

PubMed Central

Archibong, Anthony E.; Ramesh, Aramandla; Niaz, Mohammad S.; Brooks, Cynthia M.; Roberson, Shannon I.; Lunstra, Donald D.

2008-01-01

The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 (F-344) rats to inhaled benzo(a)pyrene (BaP), a ubiquitous environmental toxicant present in cigarette smoke, automobile exhaust fumes and industrial emissions. Rats were assigned randomly to a treatment or control group. Treatment consisted of exposure of rats via nose-only inhalation to 75μg BaP/m3, 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately on day 60 of exposures (time 0) and subsequently at 24, 48, and 72 hours, to assess the effect of exposures to BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Mean testis weight, total weight of tubules and total tubular length per paired testes were reduced 33% (P< 0.025), 27% (P < 0.01) and 39%, respectively in exposed rats (P < 0.01) compared with UNC rats. The number of homogenization-resistant spermatids was significantly reduced in BaP-exposed versus UNC rats. Plasma testosterone and intra-testicular testosterone (ITT) concentrations were significantly decreased by BaP compared with those of UNC rats. The decreases in circulating plasma testosterone were accompanied by concomitant increases in plasma LH concentrations in BaP-exposed versus control rats (P < 0.05). These data suggest that 60 days exposure to inhaled BaP contribute to reduced testicular endocrine and spermatogenic functions in exposed rats. PMID:18441403

Cadmium chloride, benzo[a]pyrene and cyclophosphamide tested in the in vitro mammalian cell micronucleus test (MNvit) in the human lymphoblastoid cell line TK6 at Covance laboratories, Harrogate UK in support of OECD draft Test Guideline 487.

PubMed

Fowler, Paul; Whitwell, James; Jeffrey, Laura; Young, Jamie; Smith, Katie; Kirkland, David

2010-10-29

The following genotoxic chemicals were tested in the in vitro micronucleus assay, at Covance Laboratories, Harrogate, UK in the human lymphoblastoid cell line TK6. Cadmium chloride (an inorganic carcinogen), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation) and cyclophosphamide (an alkylating agent requiring metabolic activation) were treated with and without cytokinesis block (by addition of cytochalasin B). This work formed part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 for the in vitro micronucleus test. The toxicity measures used, capable of detecting both cytostasis and cell death, were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index or cytokinesis blocked proliferation index in the presence of cytokinesis block. All of the chemicals tested gave significant increases in the percentage of micronucleated cells with and without cytokinesis block at concentrations giving approximately 60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcomes from this series of tests support the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in the in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P-diphtheria toxoid conjugate.

PubMed

Schellenberger, Mario T; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Schroeder, Henri; Muller, Claude P

2013-09-01

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P-diphtheria toxoid (B[a]P-DT) conjugate vaccine were sub-acutely exposed to 2mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P-DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. Copyright © 2013 Elsevier Inc. All rights reserved.

Toxicological effects of benzo(a)pyrene, DDT and their mixture on the green mussel Perna viridis revealed by proteomic and metabolomic approaches.

PubMed

Song, Qinqin; Chen, Hao; Li, Yuhu; Zhou, Hailong; Han, Qian; Diao, Xiaoping

2016-02-01

Benzo(a)pyrene (BaP) and dichlorodiphenyltrichloroethane (DDT) are persistent organic pollutants and environmental estrogens (EEs) with known toxicity towards the green mussel, Perna viridis. In this study, the toxic effects of BaP (10 µg/L) and DDT (10 µg/L) and their mixture were assessed in green mussel gills with proteomic and metabolomic approaches. Metabolic responses indicated that BaP mainly caused disturbance in osmotic regulation by significantly decrease in branched chain amino acids, dimethylamine and dimethylglycine in gills of male green mussels after exposure for 7 days. DDT mainly caused disturbance in osmotic regulation and energy metabolism by differential alteration of betaine, dimethylamine, dimethylglycine, amino acids, and succinate in gills of male green mussels. However, the mixture of BaP and DDT didn't show obvious metabolite changes. Proteomic analysis showed different protein expression profiles between different treatment groups, which demonstrated that BaP, DDT and their mixture may have different modes of action. Proteomic responses revealed that BaP induced cell apoptosis, disturbance in protein digestion and energy metabolism in gills of green mussels, whereas DDT exposure altered proteins that were associated with oxidative stress, cytoskeleton and cell structure, protein digestion and energy metabolism. However, the mixture of BaP and DDT affected proteins related to the oxidative stress, cytoskeleton and cell structure, protein biosynthesis and modification, energy metabolism, growth and apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Can we use modelling methodologies to assess airborne benzo[a]pyrene from biomonitors? A comprehensive evaluation approach

NASA Astrophysics Data System (ADS)

Ratola, N.; Jiménez-Guerrero, P.

2015-09-01

Biomonitoring data available on levels of atmospheric polycyclic aromatic hydrocarbons (PAHs) in pine needles from the Iberian Peninsula was used to estimate air concentrations of benzo[a]pyrene (BaP) and, at the same time, fuelled the comparison with chemistry transport model representations. Simulations with the modelling system WRF + CHIMERE were validated against data from the European Monitoring and Evaluation Programme (EMEP) air sampling network and using modelled atmospheric concentrations as a consistent reference in order to compare the performance of vegetation-to-air estimating methods. A spatial and temporal resolution of 9 km and 1 h was implemented. The field-based database relied on a pine needles sampling scheme comprising 33 sites in Portugal and 37 sites in Spain complemented with the BaP measurements available from the EMEP sites. The ability of pine needles to act as biomonitoring markers for the atmospheric concentrations of BaP was estimated converting the levels obtained in pine needles into air concentrations by six different approaches, one of them presenting realistic concentrations when compared to the modelled atmospheric values. The justification for this study is the gaps still existing in the knowledge of the life cycles of semi-volatile organic compounds (SVOCs), particularly the partition processes between air and vegetation. The strategy followed in this work allows the definition of the transport patterns (e.g. dispersion) established by the model for atmospheric concentrations and the estimated values in vegetation.

Benzo[a]pyrene impedes self-renewal and differentiation of mesenchymal stem cells and influences fracture healing.

PubMed

Zhou, Yiqing; Jiang, Rong; An, Liqin; Wang, Hong; Cheng, Sicheng; Qiong, Shi; Weng, Yaguang

2017-06-01

Mesenchymal stem cells (MSCs) are implicated in the bone-forming process during fracture repair. Benzo[a]pyrene (BaP)-a cigarette smoke component and powerful motivator of the aryl hydrocarbon receptor (Ahr)-unfavorably influences bone condition and osteoblast differentiation. The first thing we noticed decreases self-renewal and differentiation of human bone marrow mesenchymal stem (hBM-MSCs) from smokers and activates Ahr signaling in MSCs by up-regulating the Ahr target gene cytochrome P450 (CYP) 1B1 expression. In vitro studies, we employed C3H10T1/2 and bone marrow mesenchymal stem cells (BM-MSCs) with BaP and discovered that BaP impaired innate properties of MSCs. Further investigation into MSCs showed that exposure to BaP activated Ahr signaling and inhibited TGF-β1/SMAD4 and TGF-β1/ERK/AKT signaling pathways. Corresponding with the outcomes, tibial fracture calluses produced by BaP-administered rats appeared to delay healing. This effect of BaP was abrogated by resveratrol, a natural Ahr antagonist, in vitro and in vivo. These data demonstrated that Ahr may play a key role in BaP-impaired innate properties by inhibiting SMAD-dependent signaling pathways TGF-β1/SMAD4 and SMAD-independent TGF-β1/ERK/AKT signaling pathways. Furthermore, resveratrol inhibited MSCs from adverse effects caused by BaP. Copyright © 2017. Published by Elsevier B.V.

Analysis of Benzo[a]pyrene in Vegetable Oils Using Molecularly Imprinted Solid Phase Extraction (MISPE) Coupled with Enzyme-Linked Immunosorbent Assay (ELISA)

PubMed Central

Pschenitza, Michael; Hackenberg, Rudolf; Niessner, Reinhard; Knopp, Dietmar

2014-01-01

This paper describes the development of a molecularly imprinted polymer-based solid phase extraction (MISPE) method coupled with enzyme-linked immunosorbent assay (ELISA) for determination of the PAH benzo[a]pyrene (B[a]P) in vegetable oils. Different molecularly imprinted polymers (MIPs) were prepared using non-covalent 4-vinylpyridine/divinylbenzene co-polymerization at different ratios and dichloromethane as porogen. Imprinting was done with a template mixture of phenanthrene and pyrene yielding a broad-specific polymer for PAHs with a maximum binding capacity (Q) of ∼32 μg B[a]P per 50 mg of polymer. The vegetable oil/n-hexane mixture (1:1, (v/v)) was pre-extracted with acetonitrile, the solvent evaporated, the residue reconstituted in n-hexane and subjected to MISPE. The successive washing with n-hexane and isopropanol revealed most suitable to remove lipid matrix constituents. After elution of bound PAHs from MISPE column with dichloromethane, the solvent was evaporated, the residue reconstituted with dimethyl sulfoxide and diluted 100-fold with methanol/water (10:90, (v/v)) for analysis of B[a]P equivalents with an ELISA. The B[a]P recovery rates in spiked vegetable oil samples of different fatty acid composition were determined between 63% and 114%. The presence of multiple PAHs in the oil sample, because of MIP selectivity and cross-reactivity of the ELISA, could yield overestimated B[a]P values. PMID:24887045

Dermal bioavailability of benzo[a]pyrene on lampblack: implications for risk assessment.

PubMed

Stroo, Hans F; Roy, Timothy A; Liban, Cris B; Kreitinger, Joseph P

2005-06-01

Lampblack is the principal source of contamination in soils at manufactured gas plant (MGP) sites where oil was used as the feedstock. Risks and cleanup criteria at these sites are determined primarily by the total carcinogenic polynuclear aromatic hydrocarbon (PAH) content, particularly the concentration of benzo[a]pyrene (BaP). Dermal contact with soils at oil-gas MGP sites is a significant component of the overall risks. Seven samples were collected from oil-gas MGP sites and the steady-state dermal fluxes were measured over 96 h in vitro. The standard dermal bioassay technique (in which 3H-BaP is added to the soil matrix) was modified to allow direct measurement of the dermal absorption of the native BaP in the samples. The experimentally derived dermal absorption factors for BaP were 14 to 107 times lower than the default assumption of 15% over 24 h (55-fold lower on average). The dermal fluxes were correlated positively to the total BaP and total carbon concentrations. The measured dermal absorption factors were compared to the default risk-assessment calculations for all seven samples. The calculated excess cancer risk was reduced as a result of using the measured absorption factors by 97% on average (with reductions ranging from 93 to 99%). This work indicates the risks at oil-gas MGP sites currently are overestimated by one to two orders of magnitude, and provides a protocol for the testing and data analysis needed to generate site-specific cleanup levels.

Phytoremediation for co-contaminated soils of chromium and benzo[a]pyrene using Zea mays L.

PubMed

Chigbo, Chibuike; Batty, Lesley

2014-02-01

A greenhouse experiment was carried out to investigate the single effect of benzo[a]pyrene (B[a]P) or chromium (Cr) and the joint effect of Cr-B[a]P on the growth of Zea mays, its uptake and accumulation of Cr, and the dissipation of B[a]P over 60 days. Results showed that single or joint contamination of Cr and B[a]P did not affect the plant growth relative to control treatments. However, the occurrence of B[a]P had an enhancing effect on the accumulation and translocation of Cr. The accumulation of Cr in shoot of plant significantly increased by ≥ 79 % in 50 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments and by ≥ 86 % in 100 mg kg(-1) Cr-B[a]P (1, 5, and 10 mg kg(-1)) treatments relative to control treatments. The presence of plants did not enhance the dissipation of B[a]P in lower (1and 5 mg kg(-1)) B[a]P contaminated soils; however, over 60 days of planting Z. mays seemed to enhance the dissipation of B[a]P by over 60 % in 10 mg kg(-1) single contaminated soil and by 28 to 41 % in 10 mg kg(-1)B[a]P co-contaminated soil. This suggests that Z. mays might be a useful plant for the remediation of Cr-B[a]P co-contaminated soil.

Evaluation of the UV/H2O2 system for treating natural water with a mixture of anthracene and benzo[a]pyrene at ultra-trace levels.

PubMed

Rubio-Clemente, Ainhoa; Chica, Edwin; Peñuela, Gustavo

2018-06-05

The presence of polycyclic aromatic hydrocarbons, such as anthracene (AN) and benzo[a]pyrene (BaP), in water has become a problem of great concern due to the detrimental health effects caused to humans and living beings. In this work, the efficiency of the UV/H 2 O 2 system for degrading the target compounds at ultra-trace levels in surface water has been evaluated. For this purpose, a previous optimization step using a face-centered central composite experimental design has been conducted, considering the effect of the UV-C irradiance and the initial concentration of H 2 O 2 . It was evidenced that under optimal operating conditions (11 mg L -1 H 2 O 2 and 0.63 mW cm -2 irradiance), AN and BaP removal percentages were higher than 99.8%. Additionally, 69.3% of the organic matter, in terms of total organic carbon, was mineralized without the production of transformation by-products more harmful than the parent compounds. These findings demonstrate the oxidation capacity of the examined system in a natural matrix for degrading micropollutants that cannot be converted through conventional treatment processes. Consequently, new horizons are opened for the effective use of the UV/H 2 O 2 system for drinking water production, providing the accomplishment of other regulated parameters related to water quality.

A novel P450-initiated biphasic process for sustainable biodegradation of benzo[a]pyrene in soil under nutrient-sufficient conditions by the white rot fungus Phanerochaete chrysosporium

PubMed Central

Bhattacharya, Sukanta S.; Syed, Khajamohiddin; Shann, Jodi; Yadav, Jagjit S.

2013-01-01

High molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) such as benzo[a]pyrene (BaP) are resistant to biodegradation in soil. Conventionally, white rot fungus Phanerochaete chrysosporium has been investigated for HMW-PAH degradation in soil primarily using nutrient-deficient (ligninolytic) conditions, albeit with limited and non-sustainable biodegradation outcomes. In this study, we report development of an alternative novel biphasic process initiated under nutrient-sufficient (non-ligninolytic) culture conditions, by employing an advanced experimental design strategy. During the initial nutrient-sufficient non-ligninolytic phase (16 days), the process showed upregulation (3.6-and 22.3-fold, respectively) of two key PAH-oxidizing P450 monooxygenases pc2 (CYP63A2) and pah4 (CYP5136A3) and formation of typical P450-hydroxylated metabolite. This along with abrogation (84.9%) of BaP degradation activity in response to a P450-specific inhibitor implied key role of these monooxygenases. The subsequent phase triggered on continued incubation (to 25 days) switched the process from non-ligninolytic to ligninolytic resulting in a significantly higher net degradation (91.6% as against 67.4% in the control nutrient-limited set) of BaP with concomitant de novo ligninolytic enzyme expression making it a biphasic process yielding improved sustainable bioremediation of PAH-contaminated soil. To our knowledge this is the first report on development of such biphasic process for bioremediation application of a white rot fungus. PMID:24051002

Biodegradation of benzo(a)pyrene by two freshwater microalgae Selenastrum capricornutum and Scenedesmus acutus: a comparative study useful for bioremediation.

PubMed

García de Llasera, Martha Patricia; Olmos-Espejel, José de Jesús; Díaz-Flores, Gabriel; Montaño-Montiel, Adriana

2016-02-01

A comparative evaluation of the removal of benzo(a)pyrene (BaP) by sorption and degradation by two microalgal species, Selenastrum capricornutum and Scenedesmus acutus was performed. The monitoring of the amount of BaP remaining in the liquid culture media and the biomass along with the appearance of three metabolites (4,5 dihydrodiol-BaP; 7,8-dihydrodiol-BaP; and 9,10 dihydrodiol-BaP) at short time periods (from 0.25 to 72 h) in cultures exposed to BaP was made by high-performance liquid chromatography (HPLC) with fluorescence and UV detection. Complete removal of BaP was achieved by the two live microalgal species: S. capricornutum at 15 h of exposure (99%) and S. acutus at 72 h of exposure (95%). Sorption is an important phenomenon for BaP removal by S. capricornutum but biodegradation is the principal means of removing BaP in live cells. The formation of metabolites by S. capricornutum is rapid and seems to be proportional to the amount of the BaP added to cultures. In contrast, in these bioassays, most of the BaP removal of S. acutus is due to sorption rather than degradation. The appearance of metabolites in the cultures is very slow and at a low amount compared to cultures of S. capricornutum. The similarities and differences existing between the two microalgae are important for the establishment of the conditions for bioremediation.

Transcriptomics Responses in Marine Diatom Thalassiosira pseudonana Exposed to the Polycyclic Aromatic Hydrocarbon Benzo[a]pyrene

PubMed Central

Lettieri, Teresa

2011-01-01

Diatoms are unicellular, photosynthetic, eukaryotic algae with a ubiquitous distribution in water environments and they play an important role in the carbon cycle. Molecular or morphological changes in these species under ecological stress conditions are expected to serve as early indicators of toxicity and can point to a global impact on the entire ecosystem. Thalassiosira pseudonana, a marine diatom and the first with a fully sequenced genome has been selected as an aquatic model organism for ecotoxicological studies using molecular tools. A customized DNA microarray containing probes for the available gene sequences has been developed and tested to analyze the effects of a common pollutant, benzo(a)pyrene (BaP), at a sub-lethal concentration. This approach in diatoms has helped to elucidate pathway/metabolic processes involved in the mode of action of this pollutant, including lipid metabolism, silicon metabolism and stress response. A dose-response of BaP on diatoms has been made and the effect of this compound on the expression of selected genes was assessed by quantitative real time-PCR. Up-regulation of the long-chain acyl-CoA synthetase and the anti-apoptotic transmembrane Bax inhibitor, as well as down-regulation of silicon transporter 1 and a heat shock factor was confirmed at lower concentrations of BaP, but not the heat-shock protein 20. The study has allowed the identification of molecular biomarkers to BaP to be later on integrated into environmental monitoring for water quality assessment. PMID:22073232

Environmental Assessment of the Muscatatuck Urban Training Center near Butlerville, Indiana, October and November 2005

USGS Publications Warehouse

Risch, Martin R.; Ulberg, Amanda L.; Robinson, Bret A.

2007-01-01

Concentrations of constituents detected in these samples were compared with regulatory standards (the Indiana Surface-Water-Quality Standards and Indiana Ground-Water-Quality Standards) and guidance criteria from the Indiana Department of Environmental Management's Risk Integrated System of Closures for contaminated soil and ground water. Standards or criteria were exceeded by 17 constituent concentrations in 11 environmental samples from 5 of the 7 geographic study areas. Standards or criteria were exceeded for 10 constituents: ammonia, arsenic, benzo(a)pyrene, beryllium, chloride, chloroform, copper, lead, sulfate, and zinc.

Microsomal P-450 induction by some secondary products from thermal oxidation of dietary lipids: epidermal hyperplasia, mutagenicity and cytochrome P-450 activities.

PubMed

Crawford, L; Wheeler, E L

1983-12-01

Distillable secondary products from roasted fowl were found to be cytotoxic but not mutagenic when assayed with Salmonella typhimurium strains TA98, TA100 and TA1537. A crudely separated fraction of the volatiles produced focal hyperplasia and damage to the epidermis of the backs of mice. The volatiles also caused an apparent synthesis of non-constitutive forms of rat hepatic cytochromes P-450 which metabolize benzo[a]pyrene B [a]P differently from the constitutive P-450.

Superfund Record of Decision Amendment (EPA Region 6): Texarkana Wood Preserving Co. , Texarkana, TX, March 13, 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

This decision document presents an amendment to the selected remedial action for the Texarkana Wood Preserving Co. Superfund Site. This amendment fundamentally changes the Record of Decision (ROD) executed by the Regional Administrator on September 25, 1990. This amended remedy will seal and contain soils contaminated with greater than 3 ppm (parts per million) benzo(a)pyrene equivalents, 2450 ppm total poly aromatic hydrocarbons (PAH), 20 ppb (parts per billion) as 2,3,7,8 TCDD equivalents and 150 ppm pentachlorophenol beneath a soil cap.

Health Risk Impacts of Exposure to Airborne Metals and Benzo(a)Pyrene during Episodes of High PM10 Concentrations in Poland.

PubMed

Widziewicz, Kamila; Rogula-Kozlowska, Wioletta; Loska, Krzysztof; Kociszewska, Karolina; Majewski, Grzegorz

2018-01-01

To check whether health risk impacts of exposure to airborne metals and Benzo(a) Pyrene during episodes of high PM10 concentrations lead to an increased number of lung cancer cases in Poland. In this work, we gathered data from 2002 to 2014 concerning the ambient concentrations of PM10 and PM10-bound carcinogenic Benzo(a)pyrene [B(a)P] and As, Cd, Pb, and Ni. With the use of the criterion of the exceedance in the daily PM10 mass concentration on at least 50% of all the analyzed stations, the PM10 maxima's were selected. Lung cancer occurrences in periods with and without the episodes were further compared. During a 12-year period, 348 large-scale smog episodes occurred in Poland. A total of 307 of these episodes occurred in the winter season, which is characterized by increased emissions from residential heating. The occurrence of episodes significantly (P < 0.05) increased the concentrations of PM10-bound carcinogenic As, Cd, Pb, Ni, and B(a)P. During these events, a significant increase in the overall health risk from those PM10-related compounds was also observed. The highest probability of lung cancer occurrences was found in cities, and the smallest probability was found in the remaining areas outside the cities and agglomerations. The link between PM pollution and cancer risk in Poland is a serious public health threat that needs further investigation. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

A novel baseline-correction method for standard addition based derivative spectra and its application to quantitative analysis of benzo(a)pyrene in vegetable oil samples.

PubMed

Li, Na; Li, Xiu-Ying; Zou, Zhe-Xiang; Lin, Li-Rong; Li, Yao-Qun

2011-07-07

In the present work, a baseline-correction method based on peak-to-derivative baseline measurement was proposed for the elimination of complex matrix interference that was mainly caused by unknown components and/or background in the analysis of derivative spectra. This novel method was applicable particularly when the matrix interfering components showed a broad spectral band, which was common in practical analysis. The derivative baseline was established by connecting two crossing points of the spectral curves obtained with a standard addition method (SAM). The applicability and reliability of the proposed method was demonstrated through both theoretical simulation and practical application. Firstly, Gaussian bands were used to simulate 'interfering' and 'analyte' bands to investigate the effect of different parameters of interfering band on the derivative baseline. This simulation analysis verified that the accuracy of the proposed method was remarkably better than other conventional methods such as peak-to-zero, tangent, and peak-to-peak measurements. Then the above proposed baseline-correction method was applied to the determination of benzo(a)pyrene (BaP) in vegetable oil samples by second-derivative synchronous fluorescence spectroscopy. The satisfactory results were obtained by using this new method to analyze a certified reference material (coconut oil, BCR(®)-458) with a relative error of -3.2% from the certified BaP concentration. Potentially, the proposed method can be applied to various types of derivative spectra in different fields such as UV-visible absorption spectroscopy, fluorescence spectroscopy and infrared spectroscopy.

Dissipation of available benzo[a]pyrene in aging soil co-contaminated with cadmium and pyrene.

PubMed

Wang, Kai; Chen, Xin-xin; Zhu, Zhi-qiang; Huang, Hua-gang; Li, Ting-qiang; Yang, Xiao-e

2014-01-01

A microcosm experiment was conducted to investigate the dissipation of available benzo[a]pyrene (BaP) in soils co-contaminated with cadmium (Cd) and pyrene (PYR) during aging process. The available residue of BaP in soil was separated into desorbing and non-desorbing fractions. The desorbing fraction contributed more to the dissipation of available BaP than the non-desorbing fraction did. The concentration of bound-residue fraction of BaP was quite low across all treatments. Within the duration of this study (250 days), transformation of BaP from available fractions to bound-residue fraction was not observed. Microbial degradation was the dominant mechanism of the dissipation of available BaP in the soil. The dissipation of available BaP was significantly inhibited with the increment in Cd level in the soil. The addition of PYR (250 mg kg(-1)) remarkably promoted the dissipation of available BaP without reducing Cd availability in the soil. The calculated half-life of available BaP in the soil prolonged with the increment in Cd level; however, the addition of PYR shortened the half-life of available BaP by 13.1, 12.7, and 32.8% in 0.44, 2.56, and 22 mg Cd kg(-1) soils, respectively. These results demonstrated that the inhibiting effect of Cd and the promoting effect of PYR on the dissipation of available BaP were competitive. Therefore, this study shows that the bioremediation process of BaP can be more complicated in co-contaminated soils.

Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

PubMed Central

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

Effects of benzo[a]pyrene on the blood and liver of Physalaemus cuvieri and Leptodactylus fuscus (Anura: Leptodactylidae).

PubMed

Fanali, Lara Zácari; Franco-Belussi, Lilian; Bonini-Domingos, Cláudia Regina; de Oliveira, Classius

2018-06-01

Benzo[a]pyrene (BaP) is a bio-accumulative toxic compound found in the atmosphere, water, and soil that may affect the life cycle of amphibians. In this study, a few contamination biomarkers, such as hepatic melanomacrophages (MMs), mast cells, erythrocyte micronuclei (MN) and white blood cells were used to determine how BaP acts in these cells in the anurans Physalaemus cuvieri and Leptodactylus fuscus. Animals of both species were divided into three treatment groups: 1 day, 7 days and 13 days, subcutaneously injected 2 mg/kg BaP diluted in mineral oil and control group with only mineral oil. After 7 days, BaP caused the frequency of MN to increase in both species while reducing melanin area. The micronucleus frequency increased due to the genotoxicity of BaP, while the decreasing melanin area may be related to the inhibition of tyrosinase activity, an enzyme responsible for regulating melanogenesis, decreasing the synthesis of melanin. The mast cell density increased in all groups and in both species as a response to the inflammatory action of BaP. These cells respond to nonspecific inflammatory effects leading, therefore, to this response in all treatments. The percentage of leukocytes remained unchanged probably due to great intraspecific variability. Additionally, the leukocyte profiles of both species were characterized and the differences were attributed to extrinsic factors. In short, BaP can affect the integrity of several organs and tissues, and cell functions leading to the conclusion that this compound is hepatotoxic, genotoxic and immunotoxic for anurans. Copyright © 2018 Elsevier Ltd. All rights reserved.

Photolysis of polycyclic aromatic hydrocarbons (PAHs) on Fe3+-montmorillonite surface under visible light: Degradation kinetics, mechanism, and toxicity assessments.

PubMed

Zhao, Song; Jia, Hanzhong; Nulaji, Gulimire; Gao, Hongwei; Wang, Fu; Wang, Chuanyi

2017-10-01

Photochemical behavior of various polycyclic aromatic hydrocarbons (PAHs) on Fe 3+ -modified montmorillonite was explored to determine their potential kinetics, pathways, and mechanism under visible light. Depending on the type of PAH molecules, the transformation rate follows the order of benzo[a]pyrene ≈ anthracene > benzo[a]anthracene > phenanthrene. Quantum simulation results confirm the crucial role of "cation-π" interaction between Fe 3+ and PAHs on their transformation kinetics. Primary intermediates, including quinones, ring-opening products and benzene derivatives, were identified by gas chromatography-mass spectrometer (GC-MS), and the possible photodegradation pathway of benzo[a]pyrene was proposed. Meanwhile, radical intermediates, such as reactive oxygen species (ROS) and free organic radicals, were detected by electron paramagnetic resonance (EPR) technique. The photolysis of selected PAHs, such as anthracene and benzo[a]pyrene, on clay surface firstly occurs by electron transfer from PAHs to Fe 3+ -montmorillonite, followed by degradation involving photo-induced ROS such as ·OH and ·O 2 - . To investigate the acute toxicity of photolysis products, the Microtox ® toxicity test was performed during the photodegradation processes of various PAHs. As a result, the photo-irradiation initially induces increased toxicity by generating reactive intermediates, such as free organic radicals, and then the toxicity gradually decreases with increasing of reaction time. Overall, the present study provides useful information to understand the fate and photo-transformation of PAHs in contaminated soils. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulation of Benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schellenberger, Mario T.; Grova, Nathalie; Willieme, Stephanie

2009-10-01

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of bothmore » T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-{gamma}, IL-12, TNF-{alpha} production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.« less

Quantitation of exposure to benzo[a]pyrene with monoclonal antibodies.

PubMed Central

Santella, R M; Hsieh, L L; Lin, C D; Viet, S; Weinstein, I B

1985-01-01

It is now possible to quantitate carcinogen adducts on DNA by highly sensitive immunoassays. These techniques are particularly useful for screening human populations for exposure to potential environmental carcinogens. We have developed a panel of monoclonal antibodies that react with benzo(a)pyrene (BP) modified DNA to be used in an enzyme linked immunoassay (ELISA) to quantitate adduct levels of both human and animal samples. BALBc/Cr mice were immunized with either DNA modified by 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (BPDE-I-DNA) complexed electrostatically to methylated bovine serum albumin or with BPDE-I-modified guanosine conjugated with bovine serum albumin (BPDE-I-G-BSA). Four stable clones were produced from the spleen cells of animals immunized with BPDE-I-DNA and one from BPDE-I-G-BSA immunized animals. All antibodies were shown to be highly specific for BPDE-I-DNA and did not crossreact with nonmodified DNA or with N-2-acetylaminofluorene or 1-aminopyrene modified DNA. The antibodies differed in their sensitivity to BPDE-II-DNA, BPDE-I-poly G, BPDE-I-tetraols and BPDE-I-dG. In general, all the antibodies showed the greatest affinity for their original antigen. Those generated against modified DNA showed highest reactivity against modified DNA while the one antibody generated against the monoadduct showed highest reactivity with the monoadduct. These antibodies are currently being used in a highly sensitive competitive ELISA to quantitate levels of BP-DNA adducts in various animal and human tissue samples. PMID:4085452

Importance of the structure and nanoporosity of organic matter on the desorption kinetics of benzo[a]pyrene in sediments.

PubMed

Huang, Youda; Zhang, Dainan; Duan, Dandan; Yang, Yu; Xiong, Yongqiang; Ran, Yong

2017-06-01

The desorption kinetics and mechanism were investigated using a Tenax extraction technique on different sediments spiked with radiocarbon-labeled benzo[a]pyrene (BaP). Five sedimentary fractions were sequentially fractionated, and the only nonhydrolyzable organic carbon fractions (NHC) were characterized using advanced solid-state 13 C nuclear magnetic resonance spectroscopy (NMR), improved six end-member model, and a CO 2 gas adsorption technique. The sediments contained high percentages of algaenan and/or sporopollenin but low percentages of black carbon and lignin. A first-order, two-compartment kinetics model described the desorption process very well (R 2  > 0.990). Although some of the organic carbon fractions were significantly related to the desorption kinetics parameters, the NHC fractions showed the highly significant correlation. Moreover, the nanoporosity or specific surface area (SSA) of the NHC fractions was highly related to their OC contents and aliphatic C (R 2  = 0.960, p < 0.01). The multiple regression equations among the desorption kinetics parameters, structural parameters, and nanoporosity were well established (R 2 =>0.999). Nanoporosity and aromatic C were the dominant contributors. Furthermore, the enhanced percentages of desorbed BaP at elevated temperatures significantly showed a linear regression with the structure and nanoporosity. To our knowledge, the above evidence demonstrates for the first time that the transfer (or diffusion) of BaP in the nanopores of condensed aromatic components is the dominant mechanism of the desorption kinetics of BaP at organic matter particle scale. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrating toxicogenomics into human health risk assessment: lessons learned from the benzo[a]pyrene case study.

PubMed

Chepelev, Nikolai L; Moffat, Ivy D; Labib, Sarah; Bourdon-Lacombe, Julie; Kuo, Byron; Buick, Julie K; Lemieux, France; Malik, Amal I; Halappanavar, Sabina; Williams, Andrew; Yauk, Carole L

2015-01-01

The use of short-term toxicogenomic tests to predict cancer (or other health effects) offers considerable advantages relative to traditional toxicity testing methods. The advantages include increased throughput, increased mechanistic data, and significantly reduced costs. However, precisely how toxicogenomics data can be used to support human health risk assessment (RA) is unclear. In a companion paper ( Moffat et al. 2014 ), we present a case study evaluating the utility of toxicogenomics in the RA of benzo[a]pyrene (BaP), a known human carcinogen. The case study is meant as a proof-of-principle exercise using a well-established mode of action (MOA) that impacts multiple tissues, which should provide a best case example. We found that toxicogenomics provided rich mechanistic data applicable to hazard identification, dose-response analysis, and quantitative RA of BaP. Based on this work, here we share some useful lessons for both research and RA, and outline our perspective on how toxicogenomics can benefit RA in the short- and long-term. Specifically, we focus on (1) obtaining biologically relevant data that are readily suitable for establishing an MOA for toxicants, (2) examining the human relevance of an MOA from animal testing, and (3) proposing appropriate quantitative values for RA. We describe our envisioned strategy on how toxicogenomics can become a tool in RA, especially when anchored to other short-term toxicity tests (apical endpoints) to increase confidence in the proposed MOA, and emphasize the need for additional studies on other MOAs to define the best practices in the application of toxicogenomics in RA.

Fate of phenanthrene, pyrene and benzo[a]pyrene during biodegradation of crude oil added to two soils.

PubMed

Smith, M J; Lethbridge, G; Burns, R G

1999-04-15

The release of 14CO2 from 9-[14C]phenanthrene, 4,5,9,10-[14C]pyrene and 7-[14C]benzo[a]pyrene, added to Brent/Fortes crude oil and mixed into a pristine sand soil (0.40% organic C) and a pristine organic soil (22.9% organic C), was determined. After 244 days at 25 degrees C, 11.1 +/- 3.5% (sand) and 17.1 +/- 0.30% (organic) phenanthrene-14C and 9.77 +/- 2.8% (sand) and 5.86 +/- 1.4% (organic) benzo[a]pyrene-14C was released. After 210 days, 3.65 +/- 0.5% (sand) and 4.43 +/- 0.33% (organic) pyrene-14C was released. Inoculation of these two soils with DC1 and PD2 (bacteria capable of accelerating the phenanthrene and pyrene mineralisation in soil in the absence of crude oil) either at day 0 or after release as 14CO2 by indigenous degraders had ceased, failed to increase or initiate further mineralisation. Thus, aged PAH residues were non-bioavailable to these metabolically competent degrading microorganisms. At the end of the first period of incubation (210 days or 244 days), the total aromatic hydrocarbons recovered using Soxhlet extraction was 0.18% (sand) and 42.8% (organic) compared with approximately 100% from bio-inhibited soils. This confirmed that the indigenous microbiological activity not only caused a limited amount of PAH mineralisation but also reduced the extractability of residues, possibly due to the generation of metabolites which were chemisorbed and bound (and non extractable) in 'aged' soils.

Elimination of polycyclic aromatic hydrocarbons from smoked sausages by migration into polyethylene packaging.

PubMed

Semanová, Jana; Skláršová, Božena; Šimon, Peter; Šimko, Peter

2016-06-15

The objective of this work was a study of interactions between a smoked meat product and plastic packaging to find a possibility of elimination of polycyclic aromatic hydrocarbons (PAH) from smoked sausages by migration into the packaging. Smoked meat sausages were packed into o-polyamide/low density polyethylene laminated film and content of four PAH was determined at 0, 15, 30, 45, 60, 75, 90, 120, 150 and 180 min by HPLC. During this time, total PAH4 content decreased from 30.1 to 5.7 μg/kg, benzo[a]anthracene decreased from 11.5 to 2.1 μg/kg, chrysene from 9.4 to 1.9 μg/kg, benzo[b]fluoranthene from 5.3 to 0.6 μg/kg and benzo[a]pyrene from 3.9 to 1.1 μg/kg while PAH4 content in non-packed sausages remained at a constant level. So, while sausages did not meet European safety limits set for PAH4 content of 12 μg/kg and 2 μg/kg for benzo[a]pyrene before packaging, these limits were met at the end of the experiment. This decrease was brought about by migration of PAH4 from sausages into low density polyethylene packaging bulk and the measure of decrease can be predicted by a kinetic equation, making it possible to calculate PAH content equal to any time of experiment as well as the time of interaction necessary to fulfil EU legislative limits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Differences in lung local dosimetry of the carcinogens benzo(a)pyrene and NNK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahl, A.R.; Muggenburg, B.A.; Thornton-Manning, J.R.

1996-12-31

A diffusion model predicts that highly lipophilic toxicants penetrate the comparatively thick epithelium of the conducting airways much more slowly than less lipophilic toxicants. To validate this model, the tracheal walls of a Beagle dog were sprayed with very small quantities of tritiated, highly lipophilic benzo(a)pyrene (BaP), moderately lipophilic pyrene, or slightly lipophilic 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone-(NNK). The concentration of the hydrocarbons and their metabolites were measured in the circulating blood for up to 6 hr, and tissue retention was determined at the end of the experiment. Differences in absorption of these compounds into blood were manifested in several independent measurements. Themore » highly lipophilic toxicant manifested: (1) a much slower penetration into azygous vein blood, the principal drainage system from the exposed area of the trachea; (2) a much slower appearance in the systemic circulation and (3) a much greater retention in the tracheal tissues at the end of the exposure. Increased retention mm in the airway mucosa allowed a grew fraction of lipophilic toxicants to be metabolized locally in the airway walls. This finding led us to conclude that, for example, if the carcinogens BaP and NNK are deposited at the same surface density on the airway mucosa, the highly lipophilic BaP will reach a far higher concentration in the airway epithelium than will the less lipophilic NNK. Such sharp differences in local dosimetry should be considered in order to improve the accuracy of risk assessment models for inhalants.« less

PAH concentrations simulated with the AURAMS-PAH chemical transport model over Canada and the USA

NASA Astrophysics Data System (ADS)

Galarneau, E.; Makar, P. A.; Zheng, Q.; Narayan, J.; Zhang, J.; Moran, M. D.; Bari, M. A.; Pathela, S.; Chen, A.; Chlumsky, R.

2013-07-01

The off-line Eulerian AURAMS chemical transport model was adapted to simulate the atmospheric fate of seven PAHs: phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene + triphenylene, and benzo[a]pyrene. The model was then run for the year 2002 with hourly output on a~grid covering southern Canada and the continental USA with 42 km horizontal grid spacing. Model predictions were compared to ~ 5000 24 h average PAH measurements from 45 sites, eight of which also provided data on particle/gas partitioning which had been modelled using two alternative schemes. This is the first known regional modelling study for PAHs over a North American domain and the first modelling study at any scale to compare alternative particle/gas partitioning schemes against paired field measurements. Annual average modelled total (gas + particle) concentrations were statistically indistinguishable from measured values for fluoranthene, pyrene and benz[a]anthracene whereas the model underestimated concentrations of phenanthrene, anthracene and chrysene + triphenylene. Significance for benzo[a]pyrene performance was close to the statistical threshold and depended on the particle/gas partitioning scheme employed. On a day-to-day basis, the model simulated total PAH concentrations to the correct order of magnitude the majority of the time. Model performance differed substantially between measurement locations and the limited available evidence suggests that the model spatial resolution was too coarse to capture the distribution of concentrations in densely populated areas. A more detailed analysis of the factors influencing modelled particle/gas partitioning is warranted based on the findings in this study.

Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA.

PubMed

Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher; Dissanayake, Thakshila; Lin, Chen; Giambasu, George Madalin; Lad, Rahul R; Wojciechowski, Filip; Amin, Shantu; Sturla, Shana J; Hudson, Robert H E; York, Darrin M; Jankowiak, Ryszard; Jones, Roger; Tretyakova, Natalia Y

2011-05-01

Endogenous 5-methylcytosine ((Me)C) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational 'hotspots' for smoking induced lung cancer. (Me)C enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5'-CCCGGCACCC GC[(15)N(3),(13)C(1)-G]TCCGCG-3', + strand) were prepared containing [(15)N(3), (13)C(1)]-guanine opposite unsubstituted cytosine, (Me)C, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2'-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE-DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N(2) position of guanine. © The Author(s) 2011. Published by Oxford University Press.

Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA

PubMed Central

Guza, Rebecca; Kotandeniya, Delshanee; Murphy, Kristopher; Dissanayake, Thakshila; Lin, Chen; Giambasu, George Madalin; Lad, Rahul R.; Wojciechowski, Filip; Amin, Shantu; Sturla, Shana J.; Hudson, Robert H.E.; York, Darrin M.; Jankowiak, Ryszard; Jones, Roger; Tretyakova, Natalia Y.

2011-01-01

Endogenous 5-methylcytosine (MeC) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational ‘hotspots’ for smoking induced lung cancer. MeC enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5′-CCCGGCACCC GC[15N3,13C1-G]TCCGCG-3′, + strand) were prepared containing [15N3, 13C1]-guanine opposite unsubstituted cytosine, MeC, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2′-deoxynucleosides, N2-BPDE-dG adducts formed at the [15N3, 13C1]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N2-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE–DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N2 position of guanine. PMID:21245046

Groundwater contamination by polycyclic aromatic hydrocarbon due to diesel spill from a telecom base station in a Nigerian City: assessment of human health risk exposure.

PubMed

Ugochukwu, Uzochukwu Cornelius; Ochonogor, Alfred

2018-03-26

Diesel pollution of groundwater poses great threat to public health, mainly as a result of the constituent polycyclic aromatic hydrocarbons (PAHs). In this study, the human health risk exposure to polycyclic aromatic hydrocarbons (PAHs) in diesel contaminated groundwater used by several families at Ring Road, Jos, Nigeria (as caused by diesel spill from a telecom base station) was assessed. Prior to the groundwater being treated, the residents were using the water after scooping off the visible diesel sheen for purposes of cooking, washing, and bathing. Until this study, it is not clear whether the groundwater contamination had resulted in sub-chronic exposure of the residents using the water to polycyclic aromatic hydrocarbons (PAHs) to the extent of the PAHs posing a health risk. The diesel contaminated groundwater and uncontaminated nearby groundwater (control) were collected and analyzed for PAHs using gas chromatography-mass spectrometry (GC-MS). The dosage of the dermal and oral ingestion entry routes of PAHs was determined. The estimation of the non-carcinogenic health risk was via hazard quotients (HQ) and the associated hazard index (HI), while the estimation of the carcinogenic health risk was via lifetime cancer risks (LCR) and the associated risk index (RI). Obtained results indicate that the exposure of the residents to the PAHs may have made them susceptible to the risk of non-carcinogenic health effects of benzo(a)pyrene and the carcinogenic health effects of benzo(a)anthracene and benzo(a)pyrene.

Seasonal variation of benzo(a)pyrene in the Spanish airborne PM10. Multivariate linear regression model applied to estimate BaP concentrations.

PubMed

Callén, M S; López, J M; Mastral, A M

2010-08-15

The estimation of benzo(a)pyrene (BaP) concentrations in ambient air is very important from an environmental point of view especially with the introduction of the Directive 2004/107/EC and due to the carcinogenic character of this pollutant. A sampling campaign of particulate matter less or equal than 10 microns (PM10) carried out during 2008-2009 in four locations of Spain was collected to determine experimentally BaP concentrations by gas chromatography mass-spectrometry mass-spectrometry (GC-MS-MS). Multivariate linear regression models (MLRM) were used to predict BaP air concentrations in two sampling places, taking PM10 and meteorological variables as possible predictors. The model obtained with data from two sampling sites (all sites model) (R(2)=0.817, PRESS/SSY=0.183) included the significant variables like PM10, temperature, solar radiation and wind speed and was internally and externally validated. The first validation was performed by cross validation and the last one by BaP concentrations from previous campaigns carried out in Zaragoza from 2001-2004. The proposed model constitutes a first approximation to estimate BaP concentrations in urban atmospheres with very good internal prediction (Q(CV)(2)=0.813, PRESS/SSY=0.187) and with the maximal external prediction for the 2001-2002 campaign (Q(ext)(2)=0.679 and PRESS/SSY=0.321) versus the 2001-2004 campaign (Q(ext)(2)=0.551, PRESS/SSY=0.449). Copyright 2010 Elsevier B.V. All rights reserved.

Evaluation of the impact of wood combustion on benzo[a]pyrene (BaP) concentrations; ambient measurements and dispersion modeling in Helsinki, Finland

NASA Astrophysics Data System (ADS)

Hellén, Heidi; Kangas, Leena; Kousa, Anu; Vestenius, Mika; Teinilä, Kimmo; Karppinen, Ari; Kukkonen, Jaakko; Niemi, Jarkko V.

2017-03-01

Even though emission inventories indicate that wood combustion is a major source of polycyclic aromatic hydrocarbons (PAHs), estimating its impacts on PAH concentration in ambient air remains challenging. In this study the effect of local small-scale wood combustion on the benzo[a]pyrene (BaP) concentrations in ambient air in the Helsinki metropolitan area in Finland is evaluated, using ambient air measurements, emission estimates, and dispersion modeling. The measurements were conducted at 12 different locations during the period from 2007 to 2015. The spatial distributions of annual average BaP concentrations originating from wood combustion were predicted for four of those years: 2008, 2011, 2013, and 2014. According to both the measurements and the dispersion modeling, the European Union target value for the annual average BaP concentrations (1 ng m-3) was clearly exceeded in certain suburban detached-house areas. However, in most of the other urban areas, including the center of Helsinki, the concentrations were below the target value. The measured BaP concentrations highly correlated with the measured levoglucosan concentrations in the suburban detached-house areas. In street canyons, the measured concentrations of BaP were at the same level as those in the urban background, clearly lower than those in suburban detached-house areas. The predicted annual average concentrations matched with the measured concentrations fairly well. Both the measurements and the modeling clearly indicated that wood combustion was the main local source of ambient air BaP in the Helsinki metropolitan area.

Adsorption of benzo(a)pyrene on to asbestos and manmade mineral fibres in an aqueous solution and in a biological model solution.

PubMed Central

Gerde, P; Scholander, P

1988-01-01

The adsorption of benzo(a)pyrene (BaP) on to three types of asbestos (chrysotile antophyllite, and amosite) and three types of manmade mineral fibres (MMMF) (rock wool, slag wool, and glass wool) in a physiological water solution was studied. Adsorption was determined from the decrease in the liquid concentration of BaP on the addition of the solid material. Results show that all the fibres weakly adsorb BaP, approximately within the same order of magnitude. The combined adsorption of BaP and phosphatidylcholine (PC) on to chrysotile and amosite asbestos and on to rock wool in aqueous solution was also studied. PC, one of the major constituents in lung surfactant, forms a separate lipid phase in water consisting of micellar liposomes or lipid bilayers. A decrease in the liquid concentration of PC was found when any of the three materials was added, indicating adsorption of the lipid phase on to the fibres. A coincident decrease in the liquid concentration of BaP was also found indicating that BaP is readily solubilised in PC and will accompany the adsorption of this compound on to the fibres. Owing to the high lipid aqueous partition coefficient of BaP, it is concluded that the direct adsorption of BaP on to the fibres will be negligible when PC is present in the system even at low concentrations. Phospholipid adsorption by the fibres and not their direct adsorption of aromatic hydrocarbons should therefore be the crucial parameter for this indirect interaction between fibres and aromatic hydrocarbons. PMID:3196662

Benzo(a)pyrene and X-rays induce reversions of the pink-eyed unstable mutation in the retinal pigment epithelium of mice.

PubMed

Bishop, A J; Kosaras, B; Sidman, R L; Schiestl, R H

2000-12-20

The pink-eyed unstable (p(un)) mutation is the result of a 70kb tandem duplication within the murine p gene. Homologous deletion/recombination of the locus to wild-type occurs spontaneously in embryos and results in pigmented spots in the fur and eye that persist for life. Such deletion events are also inducible by a variety of DNA damaging agents, as we have observed previously with the fur spot assay. Here, we describe the use of the retinal pigment epithelium (RPE) of the eye to detect reversion events induced with two differently acting agents. Benzo(a)pyrene (B(a)P) induces a high frequency, and X-ray exposure a more modest increase, of p(un) reversion in both the fur and the eye. The eye-spot assay requires fewer mice for significant results than the fur spot assay. Previous work had elucidated the cell proliferation pattern in the RPE and a position effect variegation phenotype in the pattern of p(un) reversions, which we have confirmed. Acute exposure to B(a)P or X-rays resulted in an increased frequency of reversion events. The majority of the spontaneous reversions lie toward the periphery of the RPE whereas induced events are found more centrally, closer to the optic nerve head. The induced distribution corresponds to the major sites of cell proliferation in the RPE at the time of exposure, and further advocates the proposal that dividing cells are at highest risk to develop deletions.

Fullerene inhibits benzo(a)pyrene Efflux from Cyprinus carpio hepatocytes by affecting cell membrane fluidity and P-glycoprotein expression.

PubMed

Chen, Qiqing; Hu, Xialin; Wang, Rui; Yuan, Jin; Yin, Daqiang

2016-05-01

P-Glycoprotein (P-gp) can protect cells by pumping out toxic compounds, and has been found widely expressed in fish tissues. Here, we illustrate the P-gp efflux ability for benzo(a)pyrene (BaP) in the hepatocytes of common carp (Cyprinus carpio) after exposing to fullerene aqueous suspension (nC60). The results revealed that nC60 increased the membrane fluidity by decreasing the ratio of saturated to unsaturated fatty acids, and increased the cholesterol contents. These findings, combined with 10-38% and 70-75% down-regulation of P-gp mRNA and protein respectively, suggested that nC60 caused inhibition on P-gp efflux transport system. Therefore, we further investigated the cellular efflux ability for BaP. Results showed unequivocally that nC60 is a potent P-gp inhibitor. The retaining BaP amounts after efflux were elevated by 1.7-2.8 fold during the 10 day exposure. Meanwhile, 5mg/L humic acid (one of the important fractions of natural organic matter, which is ubiquitous in aquatic environment) alleviated the nC60 damage to hepatocytes in terms of oxidative damage, cholesterol increment, and P-gp content reduction; and finally attenuated the suppressed P-gp efflux ability. Collectively, this study provides the first evidence of nC60 toxicity to P-gp functionality in fish and illustrates the possible mechanism of the suppressed P-gp efflux ability for BaP. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism for Clastogenic Activity of Naphthalene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buchholz, Bruce A.

2016-06-24

Naphthalene incubations form DNA adducts in vitro in a dose dependent manner in both mouse and rat tissues. Rodent tissue incubations with naphthalene indicate that naphthalene forms as many DNA adducts as Benzo(a)pyrene, a known DNA binding carcinogen. The mouse airway has the greatest number of DNA adducts, corresponding to the higher metabolic activation of naphthalene in this location. Both rat tissues, the rat olfactory (tumor target) and the airways (non-tumor target), have similar levels of NA-DNA adducts, indicating that short term measures of initial adduct formation do not directly correlate with sites of tumor formation in the NTP bioassays.

Benzo(a)pyrene-7,8-dihydrodiol 9,10-oxide adenosine and deoxyadenosine adducts: structure and stereochemistry.

PubMed

Jeffrey, A M; Grzeskowiak, K; Weinstein, I B; Nakanishi, K; Roller, P; Harvey, R G

1979-12-14

The structure and absolute stereoconfigurations of four adenosine adducts with (+/-)-7 alpha,8 beta-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and their deoxyadenosine analogs have been determined. They result from both cis and trans addition of the N6 amino group of ademine to the 10 position of both enantiomers of BDPE. This was determined from studies of the nuclear magnetic resonance spectra, mass spectra, and circular dichroism spectra, as well as from their pKa values and chemical reactivities.

Synthesis of polycyclic aromatic hydrocarbon-protein conjugates for preparation and immunoassay of antibodies.

PubMed

Glushkov, Andrey N; Kostyanko, Mikhail V; Cherno, Sergey V; Vasilchenko, Ilya L

2002-04-01

The method is described dealing with the synthesis of conjugates protein-polycyclic aromatic hydrocarbons (PAHs), highly soluble in water, stable without special stabilizers and containing the minimum quantity of cross-linked products. The reaction of protein with PAH containing an aldehyde group, has been carried out in an alkaline solution, and stabilization of the conjugate has been achieved by reduction with sodium borohydride in the presence of a compound blocking the formation of an insoluble polymeric fraction. The efficiency of synthesized conjugates for the induction and immunoassay of Abs to PAH for benzo[a]pyrene is shown.

Analysis of the impregnation of ZnO:Mn2+ nanoparticles on cigarette filters for trapping polycyclic aromatic hydrocarbons (PAHs)

NASA Astrophysics Data System (ADS)

Estrada-Izquierdo, Irma; Sánchez-Espindola, Esther; Uribe-Hernández, Raúl; Ramón-Gallegos, Eva

2012-10-01

Each cigarette can generate 1149 ng of a mixture of 14 polycyclic aromatic hydrocarbons, of which there are a lot of information about its harmful effects on the environment and human health, they are considered mutagenic, teratogenic and carcinogenic. In this paper we tested ZnO:Mn2+ nanoparticles, attached to the filters of cigarettes. The first results showed that the filtration system was able to catch the Benzo(a)pyrene contained in cigarette smoke; but more tests are needed to quantify the efficiency with greater accuracy over other polycyclic aromatic hydrocarbons.

Pacific Northwest Laboratory annual report for 1984 to the DOE Office of Energy Research. Part 1. Biomedical sciences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Felton, D.L.

1985-02-01

Research progress is reported in the following areas: (1) evaluation of possible health effects among nuclear workers; (2) dose-effect relationship studies of carcinogenesis from both nuclear materials and complex mixtures; (3) microbial mutagenesis studies with 6-aminochrysene and benzo(a)pyrene in coal-derived complex mixtures; and (4) a variety of studies relating to noncarcinogenic and nonmutagenic endpoints, including teratology, perinatal studies and studies to determine absorption, metabolism, and doses to critical tissues and organs of coal-derived mixtures and radionuclides. Items have been individually abstracted for the data base. (ACR)

Benzo[a]pyrene activates an AhR/Src/ERK axis that contributes to CYP1A1 induction and stable DNA adducts formation in lung cells.

PubMed

Vázquez-Gómez, G; Rocha-Zavaleta, L; Rodríguez-Sosa, M; Petrosyan, P; Rubio-Lightbourn, J

2018-06-01

Benzo[a]pyrene (B[a]P), the most extensively studied carcinogen in cigarette smoke, has been regarded as a critical mediator of lung cancer. It is known that B[a]P-mediated Aryl hydrocarbon Receptor (AhR) activation stimulates the mitogen activated protein kinases (MAPK) signaling cascade in different cell models. MAPK pathway disturbances drive alterations in cellular processes, such as differentiation, proliferation, and apoptosis, and the disturbances may also modify the AhR pathway itself. However, MAPK involvement in B[a]P metabolic activation and toxicity in lung tissues is not well understood. Here, we used a non-transformed human bronchial epithelial lung cell line, BEAS-2B, to study the participation of ERK 1/2 kinases in the metabolic activation of B[a]P and in its related genotoxic effects. Our results indicate that B[a]P is not cytotoxic to BEAS-2B cells at relatively low concentrations, but it enhances CYP1A1 gene transcription and protein induction. Additionally, B[a]P promotes Src and ERK 1/2 phosphorylation. Accordingly, inhibition of both Src and ERK 1/2 phosphorylation decreases CYP1A1 protein induction, AhR nuclear translocation and production of B[a]P adducts. Together, these data suggest a crosstalk between AhR and the members of the MAPK pathway, ERK 1/2 mediated by Src kinase. This interaction is important for the adequate AhR pathway signaling that in turn induces transcription and protein induction of CYP1A1 and B[a]P-induced DNA damage in BEAS-2B cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between total polar components and polycyclic aromatic hydrocarbons in fried edible oil.

PubMed

An, Ke-Jing; Liu, Yu-Lan; Liu, Hai-Lan

2017-09-01

Deep-fried dough sticks (a Chinese traditional breakfast) were fried individually in peanut, sunflower, rapeseed, rice bran, soybean and palm oil without any time lag for 32 h (64 batches fried, each for 30 min) and fried oil samples were obtained every 2 h. The frying-induced changes in the levels of total polar compounds (TPC) and polycyclic aromatic hydrocarbons (PAHs) were investigated by edible oil polar compounds (EOPC) fast separation chromatographic system and gas chromatography-mass spectrometry (GC-MS), respectively. The correlations were analysed of TPC with benzo[a]pyrene (BaP), TPC and PAH4 (benzo[a]anthracene, chrysene, benzo[b]fluoranthene and benzo[a]pyrene) as well as TPC with PAH16 (USEPA 16 PAHs). The results revealed that the levels of TPC and PAHs in fried oil considerably increased with frying time, and the type of oil affected their formation, which could inform the choice of oil for frying. The total BaP equivalents (∑BaPeq) concentrations in fresh oil and in oil whose TPC exceeded 27% were 2.14-13.48 and 5.78-10.80 μg kg -1 , respectively, which means that the carcinogenic potency of frying oil was more pronounced than that of fresh oil. In addition, the TPC concentration was significantly correlated with the concentrations of the sum of the 16 PAHs, PAH4 and BaP, so that the levels of PAHs could be predicted according to the levels of TPC in fried oil. In European standards, the rejection point for TPC in frying oil should be recalculated when considered PAHs. In all, the concentration of PAHs is a vital factor for ensuring the safety of frying oil.

Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States.

PubMed

Sinha, Rashmi; Park, Yikyung; Graubard, Barry I; Leitzmann, Michael F; Hollenbeck, Albert; Schatzkin, Arthur; Cross, Amanda J

2009-11-01

The authors examined associations between meat consumption (type, cooking method, and related mutagens), heme iron, nitrite/nitrate, and prostate cancer in a cohort of 175,343 US men aged 50-71 years. During 9 years of follow-up (1995-2003), they ascertained 10,313 prostate cancer cases (1,102 advanced) and 419 fatal cases. Hazard ratios comparing the fifth intake quintile with the first revealed elevated risks associated with red and processed meat for total (red meat: hazard ratio (HR) = 1.12, 95% confidence interval (CI): 1.04, 1.21; processed meat: HR = 1.07, 95% CI: 1.00, 1.14) and advanced (red meat: HR = 1.31, 95% CI: 1.05, 1.65; processed meat: HR = 1.32, 95% CI: 1.08, 1.61) prostate cancer. Heme iron, barbecued/grilled meat, and benzo[a]pyrene were all positively associated with total (HR = 1.09 (95% CI: 1.02, 1.17), HR = 1.11 (95% CI: 1.03, 1.19), and HR = 1.09 (95% CI: 1.00, 1.18), respectively) and advanced (HR = 1.28 (95% CI: 1.03, 1.58), HR = 1.36 (95% CI: 1.10, 1.69), and HR = 1.28 (95% CI: 1.00, 1.65), respectively) disease. Nitrite (HR = 1.24, 95% CI: 1.02, 1.51) and nitrate (HR = 1.31, 95% CI: 1.07, 1.61) intakes were associated with advanced prostate cancer. There were no clear associations for fatal prostate cancer. Red and processed meat may be positively associated with prostate cancer via mechanisms involving heme iron, nitrite/nitrate, grilling/barbecuing, and benzo[a]pyrene.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Transcriptional responses of Acropora hyacinthus embryo under the benzo(a)pyrene stress by deep sequencing.

PubMed

Xiao, Rong; Zhou, Hailong; Chen, Chien-Min; Cheng, Huamin; Li, Hongwu; Xie, Jia; Zhao, Hongwei; Han, Qian; Diao, Xiaoping

2018-04-24

Coral embryos are a critical and sensitive period for the early growth and development of coral. Benzo(a)pyrene (BaP) is widely distributed in the ocean and has strong toxicity, but there is little information on the toxic effects to coral embryos exposed to this widespread environmental contaminant. Thus, in this study, we utilized the Illumina Hiseq™ 4000 platform to explore the gene response of Acropora hyacinthus embryos under the BaP stress. A total of 130,042 Unigenes were obtained and analyzed, and approximately 37.67% of those matched with sequences from four different species. In total, 2606 Unigenes were up-regulated, and 3872 Unigenes were down-regulated. After Gene Ontology (GO) annotation, the results show that the "cellular process" and "metabolic process" were leading in the category of biological processes, which the "binding" and "catalytic activity" were the most abundant subcategories in molecular function. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the most differentially expressed genes (DEGs) were enriched, as well as down-regulated in the pathways of oxidative phosphorylation, metabolism of xenobiotics, immune-related genes, apoptosis and human disease genes. At the same time, 388,197 of Single-nucleotide Polymorphisms (SNPs) and 6164 of Simple Sequence Repeats (SSRs) were obtained, which can be served as the richer and more valuable SSRs molecular markers in the future. The results of this study can help to better understand the toxicological mechanism of coral embryo exposed to BaP, and it is also essential for the protection and restoration of coral reef ecosystem in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative study of bioconcentration and EROD activity induction in the Japanese flounder, red sea bream, and Java medaka exposed to polycyclic aromatic hydrocarbons.

PubMed

Cheikyula, J Orkuma; Koyama, Jiro; Uno, Seiichi

2008-06-01

Japanese flounder (Paralichthys olivaceus), red sea bream (Pagrus major), and Java medaka (Oryzias javanicus) were exposed to water borne polycyclic aromatic hydrocarbons (PAHs) for 10 days to compare PAH bioconcentration and P450 enzyme induction by ethoxyresorufin-O-deethylase (EROD) activity for use in oil spill biomonitoring in Asian waters. Target exposure concentration for phenanthrene, pyrene, and chrysene were 30 microg/L each, while benzo[a]pyrene was 3.0 microg/L. Phenanthrene and pyrene were accumulated in the flounder and red sea bream; chrysene was found only in the livers of the red sea bream, while Java medaka accumulated the high molecular weight benzo[a]pyrene along with the other PAHs. Total PAH concentrations increased with duration of exposure in the red sea bream from 184+/-37 ng/g wet weight (w.w.) in day 2 to 572+/-72 ng/g (w.w.) in day 10; It, however, decreased in the other two species. Among the three fish species, Java medaka had the highest initial total PAH concentration of 388+/-62 ng/g (w.w.); this was, however, reduced to the lowest final concentration of 52.3+/-3 ng/g (w.w.). It also had the highest EROD activity of 4.2+/-2.8 n mol/min/mg protein compared to the lowest of 0.11+/-0.03 n mol/min/mg protein in the Japanese flounder. Java medaka with high EROD activity induction and bioaccumulation of all PAHs will be suitable for PAH biomonitoring in Asian waters. Due to its high PAH bioconcentration red sea bream is also recommended for consideration for biomonitoring and PAH chronic toxicity tests.

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

PubMed Central

Labib, Sarah; Bourdon-Lacombe, Julie; Kuo, Byron; Buick, Julie K.; Lemieux, France; Williams, Andrew; Halappanavar, Sabina; Malik, Amal; Luijten, Mirjam; Aubrecht, Jiri; Hyduke, Daniel R.; Fornace, Albert J.; Swartz, Carol D.; Recio, Leslie; Yauk, Carole L.

2015-01-01

Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work. PMID:25605026

Air quality assessment of benzo(a)pyrene from asphalt plant operation.

PubMed

Gibson, Nigel; Stewart, Robert; Rankin, Erika

2012-01-01

A study has been carried out to assess the contribution of Polycyclic Aromatic Hydrocarbons (PAHs) from asphalt plant operation, utilising Benzo(a)pyrene (BaP) as a marker for PAHs, to the background air concentration around asphalt plants in the UK. The purpose behind this assessment was to determine whether the use of published BaP emission factors based on the US Environmental Protection Agency (EPA) methodology is appropriate in the context of the UK, especially as the EPA methodology does not give BaP emission factors for all activities. The study also aimed to improve the overall understanding of BaP emissions from asphalt plants in the UK, and determine whether site location and operation is likely to influence the contribution of PAHs to ambient air quality. In order to establish whether the use of US EPA emissions factors is appropriate, the study has compared the BaP emissions measured and calculated emissions rates from two UK sites with those estimated using US EPA emission factors. A dispersion modelling exercise was carried out to show the BaP contribution to ambient air around each site. This study showed that, as the US EPA methodology does not provide factors for all emission sources on asphalt plants, their use may give rise to over- or under-estimations, particularly where sources of BaP are temperature dependent. However, the contribution of both the estimated and measured BaP concentrations to environmental concentration were low, averaging about 0.05 ng m(-3) at the boundary of the sites, which is well below the UK BaP assessment threshold of 0.25 ng m(-3). Therefore, BaP concentrations, and hence PAH concentrations, from similar asphalt plant operations are unlikely to contribute negatively to ambient air quality.

Sensitivity analysis of biodiesel blends on Benzo[a]pyrene and main emissions using MOVES: A case study in Temuco, Chile.

PubMed

Pino-Cortés, Ernesto; Díaz-Robles, Luis A; Cubillos, Francisco; Fu, Joshua S; Vergara-Fernández, Alberto

2015-12-15

Temuco is one of the most highly wood-smoke polluted cities in Chile; however, the diesel mobile sources are growing very fast in the past 10 years and so far very few studies have been done. The main goal of this research was to develop a 2013 emission inventory of criteria pollutants and Benzo[a]pyrene (BaP) and to evaluate the use of six biodiesel blends of 0%, 1%, 4%, 8%, 12%, and 20% by volume of fuel in diesel motors from the vehicle fleet within the mentioned areas using the Motor Vehicle Emission Simulator (MOVES). Input parameters for the base year 2005 were estimated to implement and adapt the model in Chile, while results of NOx, PM10, PM2.5, NH3, CO2 equivalent and SO2 were compared with the Chilean Emission Inventory estimated by the model "Methodology for the Calculation of Vehicle Emissions." The 2013 emissions reduced with respect to 2005, in the majority of the contaminants analyzed, despite the 47% increase in the annual miles traveled. Using biodiesel blends, an emission reduction was estimated at up to 15% in particulate matter, BaP, and CO for the year 2013, as well as an increment of 2% in NOx emissions, attributed to low sulfur content (50 ppm) in the diesel and the antiquity of the vehicle fleet. The results obtained gave evidence of the influence of the biodiesel use in the pollutant emissions to improve the Chilean air quality, as well as providing a strategy for this air quality management. Copyright © 2015 Elsevier B.V. All rights reserved.

Exposure of sea bream (Sparus aurata) to toxic concentrations of benzo[a]pyrene: possible human health effect.

PubMed

Zena, R; Speciale, A; Calabrò, C; Calò, M; Palombieri, D; Saija, A; Cimino, F; Trombetta, D; Lo Cascio, P

2015-12-01

Polycyclic aromatic hydrocarbons (PAHs) can accumulate in the food chain, due to their lipophilic properties. Fish can accumulate contaminants including PAHs and frequent consumption of such contaminated fish can pose risk to human health. The aim of this study was to clarify if acute exposure of sea bream (Sparus aurata, a fish species of great economic importance in the Atlantic and Mediterranean areas) to a PAH, benzo[a]pyrene (B[a]P), at a dose that can induce CYP1A and pathological changes in fish gills, liver and muscle, can induce accumulation in muscle. We investigated the cytotoxic effects (as changes in cell viability, DNA laddering and glutathione content) of in vitro exposure of human peripheral blood mononuclear cells (PBMCs) to organic extracts obtained from muscle of sea breams previously exposed via water to B[a]P (2mg/l, for 12, 24 and 72 h). At this level of exposure, B[a]P caused morphological changes, inflammatory response and CYP1A induction not only in sea bream gills and liver but also in muscle; furthermore, in fish muscle we observed a substantial B[a]P accumulation, which may be associated with the increased CYP1A activity in liver and especially in muscle. However, when PBMCs were exposed to organic extracts obtained from sea bream muscle contaminated with B[a]P, a toxic, although modest effect was revealed, consisting in a significant decrease in cell glutathione levels without alterations in cell viability and DNA laddering. This suggests that consumption of sea breams from B[a]P contaminated waters might represent a risk for human health. Copyright © 2015 Elsevier Inc. All rights reserved.

Embryotoxic effects of benzo[a]pyrene, chrysene and 7,12-dimethylbenz[a]-anthracene in petroleum hydrocarbon mixtures in mallard ducks

USGS Publications Warehouse

Hoffman, D.J.; Gay, M.L.

1981-01-01

Studies with different avian species have revealed that surface applications of microliter amounts of some crude and fuel oils that coat less than 70% of the egg surface result in considerable reduction in hatching with teratogenicity and stunted growth. Other stUdies have shown that the embryo toxicity is dependent on the aromatic hydrocarbon content, further suggesting that the toxicity is due to causes other than asphyxia. In the present study the effects of three polycyclic aromatic hydrocarbons identified in petroleum were examined on mallard (Anas platyrhynchos) embryo development. Addition of benzo[a]pyrene (BaP), chrysene, or 7,7 2-dimethylbenz[ a]anthracene (DMBA) to a synthetic petroleum hydrocarbon mixture of known composition and relatively low embryotoxicity resulted in embryo toxicity that was enhanced or equal to that of crude oil when 10 :I was applied externally to eggs at 72 h of development. The order of ability to enhance embryo toxicity was DMBA > BaP > chrysene. The temporal pattern of embryonic death was similar to that reported after exposure to crude oil, with additional mortality occurring after outgrowth of the chorioallantois. Retarded growth, as reflected by embryonic body weight, crown-rump length, and bill length, was accompanied by teratogenicity. Abnormal embryos exhibited extreme stunting; eye, brain, and bill defects; and incomplete ossification. Gas chromatographic-mass spectral analysis of externally treated eggs showed the passage of aromatic hydrocarbons including chrysene through the shell and shell membranes to the developing embryos. These findings suggest that the presence of polycyclic aromatic hydrocarbons in petroleum, including BaP, chrysene, and DMBA, significantly enhances the overall embryotoxicity in avian species.

Cytochrome P4501A induction, benzo[a]pyrene metabolism, and nucleotide adduct formation in fish hepatoma cells: Effect of preexposure to 3,3',4,4',5-pentachlorobiphenyl

USGS Publications Warehouse

Smeets, J.M.W.; Voormolen, A.; Tillitt, D.E.; Everaarts, J.M.; Seinen, W.; Vanden Berg, M.D.

1999-01-01

In PLHC-1 hepatoma cells, benzo[a]pyrene (B[a]P) caused a maximum induction of cytochrome P4501A (CYP1A) activity, measured as ethoxyresorufin O-deethylation (EROD), after 4 to 8 h of exposure, depending on the B[a]P concentration. The decline of EROD activity at longer exposure times was probably caused by the rapid metabolism of B[a]P in this system (57% metabolism within 4 h incubation). In subsequent experiments, PLHC-1 cells were preinduced with PCB 126 for 24 h and then received a dose of 10, 100, or 1,000 nM 3H-B[a]P. A 1-nM concentration of PCB 126 caused an 80-fold induction of CYP1A activity, resulting in an increase in B[a]P metabolism of less than 10%, except at the highest concentration of B[a]P (1,000 nM), where a 50% increase was observed. In another experiment, an 80-fold induction of CYP1A activity caused a 20% increase in the metabolism of B[a]P (100 nM), and RNA adduct formation was increased approximately twofold. These results indicate that, at exposure concentrations up to 100 nM B[a]P, CYP1A activity is not rate limiting for B[a]P metabolism. Furthermore, CYP1A seems to also he specifically involved in B[a]P activation in PLHC-1 cells. However, CYP1A induction causes only a relatively small increase in activation, probably because of the action of other enzymes involved in B[a]P activation and deactivation.

Exploring relationships between outdoor air particulate-associated polycyclic aromatic hydrocarbon and PM 2.5: A case study of benzo(a)pyrene in California metropolitan regions

NASA Astrophysics Data System (ADS)

Lobscheid, Agnes B.; McKone, Thomas E.; Vallero, Daniel A.

Polycyclic aromatic hydrocarbons (PAHs) and particulate matter (PM) are co-pollutants emitted as by-products of combustion processes. Convincing evidence exists for PAHs as a primary toxic component of fine PM (PM 2.5). Because PM 2.5 is listed by the US EPA as a "Criteria Pollutant", it is monitored regularly at sites nationwide. In contrast, very limited data is available on measured ambient air concentrations of PAHs. However, between 1999 and 2001, ambient air concentrations of PM 2.5 and benzo(a)pyrene (BaP) are available for California locations. We use multivariate linear regression models (MLRMs) to predict ambient air levels of BaP in four air basins based on reported PM 2.5 concentrations and spatial, temporal and meteorological variables as variates. We obtain an R2 ranging from 0.57 to 0.72 among these basins. Significant variables ( p<0.05) include the average daily PM 2.5 concentration, wind speed, temperature and relative humidity, and the coastal distance as well as season, and holiday or weekend. Combining the data from all sites and using only these variables to estimate ambient BaP levels, we obtain an R2 of 0.55. These R2-values, combined with analysis of the residual error and cross validation using the PRESS-statistic, demonstrate the potential of our method to estimate reported outdoor air PAH exposure levels in metropolitan regions. These MLRMs provide a first step towards relating outdoor ambient PM 2.5 and PAH concentrations for epidemiological studies when PAH measurements are unavailable, or limited in spatial coverage, based on publicly available meteorological and PM 2.5 data.

Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes.

PubMed

Li, Jingxia; Zhang, Dongyun; Stoner, Gary D; Huang, Chuanshu

2008-04-01

The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-kappaB or the PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-alpha (TNF-alpha) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects. (c) 2007 Wiley-Liss, Inc.

Differential Effects of Black Raspberry and Strawberry Extracts on BaPDE-Induced Activation of Transcription Factors and Their Target Genes

PubMed Central

Li, Jingxia; Zhang, Dongyun; Stoner, Gary D.; Huang, Chuanshu

2013-01-01

The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor κB (NF-κB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-κB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70S6K and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-κB or the PI-3K/Akt-p70S6K and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-α (TNF-α) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects. PMID:18085529

Temporal changes of ethoxyresorufin-o-deethylase (EROD) activities and lysosome accumulation in intestine of fish on chronic exposure to dietary benzo[a]pyrene: linking erod induction to cytological effects.

PubMed

Yuen, Bonny B H; Au, Doris W T

2006-10-01

Temporal changes of intestinal and hepatic ethoxyresorufin-O-deethylase (EROD) activities and quantitative changes of secondary and tertiary (e.g., 2 degrees/3 degrees) lysosomes in enterocytes were compared for the juvenile grouper (Epinephelus coioides) on chronic exposure to foodborne benzo[a]pyrene (BaP) at two environmentally realistic levels (0.25 and 12.5 microg/g fish/d) over a four-week exposure and four-week depuration period. Intestinal EROD induction was rapid (within 3 d) and sustained in the BaP-exposed fish, while a fast recovery (within one week) was observed on withdrawal of BaP intake. A dose-response relationship was demonstrated between intestinal EROD activities and the levels of foodborne BaP. Conversely, hepatic EROD induction was weak and subsided rapidly in the exposed fish, signifying that hepatic EROD activity is not a good indicator of oral intake of BaP. Significant increase of 2 degrees/3 degrees lysosomes, as measured by Vv(lysosome, mucosa), was detected in young enterocytes of fish in the high-dosing group (12.5 microg/g fish/d) at exposure day 3 and persisted until recovery week 2. Importantly, intestinal EROD activity was significantly correlated to 2 degrees/3 degrees lysosome accumulation in enterocytes (r = 0.571, p < 0.001). These results further corroborate our earlier findings that induction of EROD activities in fish do not merely indicate exposure to BaP but also are correlated to harmful biological effects. We recommend the use of these two biochemical and cytological changes in intestines as specific biomarkers to indicate current and recent exposure of fish to BaP via oral intake.

Induction of CYP1A1 and CYP1B1 by benzo(k)fluoranthene and benzo(a)pyrene in T-47D human breast cancer cells: Roles of PAH interactions and PAH metabolites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spink, David C.; Wu, Susan J.; Spink, Barbara C.

2008-02-01

The interactions of polycyclic aromatic hydrocarbons (PAH) and cytochromes P450 (CYP) are complex; PAHs are enzyme inducers, substrates, and inhibitors. In T-47D breast cancer cells, exposure to 0.1 to 1 {mu}M benzo(k)fluoranthene (BKF) induced CYP1A1/1B1-catalyzed 17{beta}-estradiol (E{sub 2}) metabolism, whereas BKF levels greater than 1 {mu}M inhibited E{sub 2} metabolism. Time course studies showed that induction of CYP1-catalyzed E{sub 2} metabolism persisted after the disappearance of BKF or co-exposed benzo(a)pyrene, suggesting that BKF metabolites retaining Ah receptor agonist activity were responsible for prolonged CYP1 induction. BKF metabolites were shown, through the use of ethoxyresorufin O-deethylase and CYP1A1-promoter-luciferase reporter assays tomore » induce CYP1A1/1B1 in T-47D cells. Metabolites formed by oxidation at the C-2/C-3 region of BKF had potencies for CYP1 induction exceeding those of BKF, whereas C-8/C-9 oxidative metabolites were somewhat less potent than BKF. The activities of expressed human CYP1A1 and 1B1 with BKF as substrate were investigated by use of HPLC with fluorescence detection, and by GC/MS. The results showed that both enzymes efficiently catalyzed the formation of 3-, 8-, and 9-OHBKF from BKF. These studies indicate that the inductive effects of PAH metabolites as potent CYP1 inducers are likely to be additional important factors in PAH-CYP interactions that affect metabolism and bioactivation of other PAHs, ultimately modulating PAH toxicity and carcinogenicity.« less

Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure to Benzo(a)pyrene

PubMed Central

McCallister, Monique M.; Li, Zhu; Zhang, Tongwen; Ramesh, Aramandla; Clark, Ryan S.; Maguire, Mark; Hutsell, Blake; Newland, M. Christopher; Hood, Darryl B.

2016-01-01

To characterize behavioral deficits in pre-adolescent offspring exposed in utero to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated with B(a)P (150, 300, 600, and 1200 µg/kg BW) or peanut oil (vehicle) on E14, 15, 16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites were examined in plasma and whole brain or cerebral cortex from exposed and control offspring. Tissue concentrations of B(a)P metabolites were (1) dose-dependent and (2) followed a time-dependence for elimination with ∼60% reduction by PND5 in the 1200 µg/kg BW experimental group. Spatial discrimination-reversal learning was utilized to evaluate potential behavioral neurotoxicity in P40–P60 offspring. Late-adolescent offspring exposed in utero to 600 and 1200 µg/kg BW were indistinguishable from their control counterparts for ability to acquire an original discrimination (OD) and reach criterion. However, a dose-dependent effect of in utero B(a)P-exposure was evident upon a discrimination reversal as exposed offspring perseverated on the previously correct response. This newly characterized behavioral deficit phenotype for the first reversal was not apparent in either the (1) OD or (2) subsequent reversal sessions relative to the respective control offspring. Furthermore, the expression of activity related-cytoskeletal-associated protein (Arc), an experience-dependent cortical protein marker known to be up-regulated in response to acquisition of a novel behavior, was greater in B(a)P-exposed offspring included in the spatial discrimination cohort versus home cage controls. Collectively, these findings support the hypothesis that in utero exposure to B(a)P during critical windows of development representing peak periods of neurogenesis results in behavioral deficits in later life. PMID:26420751

Cytological changes in association with ethoxyresorufin o-deethylase induction in fish upon dietary exposure to benzo[a]pyrene.

PubMed

Au, Doris W T; Chen, Ping; Pollino, Carmel A

2004-04-01

Juvenile areolated grouper (Epinephelus areolatus) were exposed to two levels of dietary benzo[a]pyrene (BaP; 0.25-12.5 microg/g body wt/d) for four weeks, followed by four weeks of depuration. Significant increase in hepatic ethoxyresorufin O-deethylase (EROD) activities was found after one week, preceding an increase in lipopigments (as measured by quantitative transmission electron microscopy) in week 2 of exposure. The EROD activities in the BaP-treated fish subsided at week 4 of exposure and throughout the depuration period. Lipopigments in the high-dose group appeared to be more persistent than that of the EROD activity during the exposure period and remained significantly higher than that of the controls at week 4. Levels of lipopigments, however, rapidly subsided on withdrawal of BaP exposure. These results appear to suggest that changes in EROD activities would precede cytological changes and that both the observed cytological and biochemical changes are reversible. Results of the present study also lend further support to our earlier findings on Solea ovata, that a significant relationship exists between EROD activity and lipopigment accumulation (as measured by volume density, absolute volume, numerical density, and absolute density; r = 0.483-0.358, p < 0.05), regardless of fish species (S. ovata and aerolated grouper) as well as the routes of exposure to BaP (intraperitoneal injection or dietary exposure). This provides strong supporting evidence that elevated EROD activities in fish liver do not merely indicate exposure to polyaromatic hydrocarbons (PAHs) but are also associated with significant biological effects. Our results showed that hepatic EROD activity and lipopigments could be used to indicate recent exposure of the fish to BaP/PAHs.

Benzo(a)pyrene quinones increase cell proliferation, generate reactive oxygen species, and transactivate the epidermal growth factor receptor in breast epithelial cells.

PubMed

Burdick, Andrew D; Davis, John W; Liu, Ke Jian; Hudson, Laurie G; Shi, Honglian; Monske, Michael L; Burchiel, Scott W

2003-11-15

Polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), are known mammary carcinogens in rodents and may be involved in human breast cancer. We have reported previously that BaP can mimic growth factor signaling and increase cell proliferation in primary human mammary epithelial cells and the human mammary epithelial cell line MCF-10A. BaP-quinones (BPQs) are important metabolites of BaP that have been associated with the production of reactive oxygen species. Using a model of epidermal growth factor (EGF) withdrawal in MCF-10A, we hypothesized that production of reactive oxygen species by BPQs could lead to the activation of the EGF receptor (EGFR). Here, we demonstrate through electron paramagnetic resonance spectroscopy and flow cytometry that 1,6-BPQ and 3,6-BPQ produce superoxide anion and hydrogen peroxide in MCF-10A cells. Furthermore, we show that BPQs increase EGFR, Akt, and extracellular signal-regulated kinase activity, leading to increased cell number in the absence of EGF. The BPQ-induced EGFR activity and associated cell proliferation were attenuated by the EGFR inhibitor AG1478, as well as by the antioxidant N-acetyl cysteine. Overexpression of catalase, but not Cu/Zn superoxide dismutase, reduced the extent of BPQ-dependent increased cell number and EGFR pathway activation. Moreover, the direct treatment of MCF-10A cells with hydrogen peroxide enhanced EGFR, Akt, and extracellular-regulated kinase phosphorylation that could be similarly inhibited by AG1478, N-acetyl cysteine, and catalase. Taken together, these data indicate that BPQs, through the generation of hydrogen peroxide, activate the EGFR in MCF-10A cells, leading to increased cell number under EGF-deficient conditions.

Benzo[a]pyrene Reduces Testosterone Production in Rat Leydig Cells via a Direct Disturbance of Testicular Steroidogenic Machinery

PubMed Central

Chung, Jin-Yong; Lee, Seung Gee; Park, Ji-Eun; Yoon, Yong-Dal; Yoo, Ki Soo; Yoo, Young Hyun

2011-01-01

Background: Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), is a ubiquitous environmental pollutant that is currently suspected of being an endocrine disruptor. The testis is an important target for PAHs, yet insufficient attention has been paid to their effects on steroidogenesis in Leydig cells. Objective: We hypothesized that long-term exposure to low concentrations of B[a]P might disrupt testosterone production in Leydig cells via an alteration of steroidogenic proteins. Results: Oral exposure to B[a]P reduced serum and intratesticular fluid testosterone levels in rats. However, we did not observe serious testicular atrophy or azoospermia, although spermatogonial apoptosis was significantly increased. Compared with control cells, Leydig cells primed with B[a]P in vivo produced less testosterone in response to human chorionic gonadotropin (hCG) or dibutyl cyclic adenosine monophosphate in vitro. Of note, the reduction of testosterone levels was accompanied by decreased expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), as well as increased levels of cytochrome P450 side chain cleavage (P450scc), in Leydig cells. The up-regulation of P450scc expression after exposure to B[a]P appears to be associated with a compensatory mechanism for producing the maximum amount of pregnenolone with the minimum amount of transported cholesterol by StAR; the down-regulation of 3β-HSD may occur because B[a]P can negatively target 3β-HSD, which is required for testosterone production. Conclusions: B[a]P exposure can decrease epididymal sperm quality, possibly by disturbing testosterone levels, and StAR may be a major steroidogenic protein that is targeted by B[a]P or other PAHs. PMID:21737371

Increased Sensitivity to Testicular Toxicity of Transplacental Benzo[a]pyrene Exposure in Male Glutamate Cysteine Ligase Modifier Subunit Knockout (Gclm−/−) Mice

PubMed Central

Nakamura, Brooke N.; Mohar, Isaac; Lawson, Gregory W.; Cortés, Mabel M.; Hoang, Yvonne D.; Ortiz, Laura; Patel, Reshma; Rau, Bogdan A.; McConnachie, Lisa A.; Kavanagh, Terrance J.; Luderer, Ulrike

2012-01-01

Polycyclic aromatic hydrocarbons (PAHs), like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants formed by the incomplete combustion of organic materials. The tripeptide glutathione (GSH) is a major antioxidant and is important in detoxification of PAH metabolites. Mice null for the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH concentrations. We investigated the effects of Gclm deletion alone on male fertility and spermatogenesis and its effect on the sensitivity of male embryos to the transplacental testicular toxicity of BaP. Gclm−/− males had dramatically decreased testicular and epididymal GCL enzymatic activity and total GSH concentrations compared with Gclm+/+ littermates. Ratios of reduced to oxidized GSH were significantly increased in Gclm−/− testes. GSH reductase enzymatic activity was increased in Gclm−/− epididymides. We observed no changes in fertility, testicular weights, testicular sperm head counts, or testicular histology and subtle changes in cauda epididymal sperm counts, motility, and morphology in Gclm−/− compared with Gclm+/+ males. Prenatal exposure to BaP from gestational day 7 to 16 was dose dependently associated with significantly decreased testicular and epididymal weights, testicular and epididymal sperm counts, and with vacuolated seminiferous tubules at 10 weeks of age. Gclm−/− males exposed prenatally to BaP had greater decreases in testicular weights, testicular sperm head counts, epididymal sperm counts, and epididymal sperm motility than Gclm+/+ littermates. These results show no effects of Gclm deletion alone on male fertility and testicular spermatogenesis and subtle epididymal effects but support increased sensitivity of Gclm−/− males to the transplacental testicular toxicity of BaP. PMID:22253057

Emissions of particle-phase polycyclic aromatic hydrocarbons (PAHs) in the Fu Gui-shan Tunnel of Nanjing, China

NASA Astrophysics Data System (ADS)

Chen, Fei; Hu, Wei; Zhong, Qin

2013-04-01

Real-world vehicle emission factors for PM10 (particulate matter with aerodynamic diameter smaller than 10 μm) and particle-phase polycyclic aromatic hydrocarbons (PAHs) from mixed vehicles were quantified in the Fu Gui-shan Tunnel of Nanjing during summer and winter of 2010. Concentrations of PM10 and sixteen particle phase polycyclic aromatic hydrocarbons (PAHs) in the entrance and exit of the tunnel were studied. The results showed that the four most abundant particular phase polycyclic aromatic hydrocarbons (PAHs) of motor vehicle were benzo[ghi]perylene, benzo[k]fluoranthene, benz[a]anthracene and benzo[a]pyrene. The emission factors for PM10 and particle-phase PAHs were 687 mg veh- 1 km- 1 and 18.853 mg veh- 1 km- 1 in summer, 714 mg veh- 1 km- 1 and 20.374 mg veh- 1 km- 1 in winter. Higher particle-phase PAH emission factors were found to be associated with a high proportion of diesel-fueled vehicles (DV). The estimated PM10 emission factor of gasoline-fueled vehicles (GV) was 513 mg veh- 1 km- 1 and the value for DV was 914 mg veh- 1 km- 1, while EFDV of particulate PAH (31.290 mg veh- 1 km- 1) was nearly 4 times higher than EFGV (9.310 mg veh- 1 km- 1). The five highest emission factors of diesel-fueled vehicles (DV) were benzo[ghi]perylene, benzo[k]fluoranthene, Indeno[1,2,3-cd]pyrene, benz[a]anthracene and benzo[a]pyrene, which was similarly found in the gasoline-fueled vehicles (GV). The sum of these five emission factors accounted for ~ 69% of the total particle-phase PAH of DV and ~ 67% of GV.

Embryonic exposure to benzo(a)pyrene inhibits reproductive capability in adult female zebrafish and correlation with DNA methylation.

PubMed

Gao, Dongxu; Lin, Jing; Ou, Kunlin; Chen, Ying; Li, Hongbin; Dai, Qinhua; Yu, Zhenni; Zuo, Zhenghong; Wang, Chonggang

2018-05-09

This study was conducted to investigate the effects of embryonic short-term exposure to benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, on ovarian development and reproductive capability in adult female zebrafish. In 1-year-old fish after embryonic exposure to BaP for 96 h, the gonadosomatic indices and the percentage of mature oocytes were significantly decreased in the 0.5, 5 and 50 nmol/L treatments. The spawned egg number, the fertilization rate and the hatching success were significantly reduced, while the malformation rate of the F1 unexposed larvae were increased. The mRNA levels of follicle-stimulating hormone, luteinizing hormone, ovarian cytochrome P450 aromatase cyp19a1a and cyp19b, estrogen receptor esr1 and esr2, and hepatic vitellogenin vtg1 and vtg2 genes, were down-regulated in adult female zebrafish that were exposed to BaP during embryonic stage. Both 17β-estradiol and testosterone levels were reduced in the ovary of adult females. The methylation levels of the gonadotropin releasing hormone (GnRH) gene gnrh3 were significantly increased in the adult zebrafish brain, and those of the GnRH receptor gene gnrhr3 were elevated both in the larvae exposed to BaP and in the adult brain, which might cause the down-regulation of the mRNA levels of gnrh3 and gnrhr3. This epigenetic change caused by embryonic exposure to BaP might be a reason for physiological changes along the brain-pituitary-gonad axis. These results suggest that short-term exposure in early life should be included and evaluated in any risk assessment of pollutant exposure to the reproductive health of fish. Copyright © 2018 Elsevier Ltd. All rights reserved.

5-Fluorouracil, colchicine, benzo[a]pyrene and cytosine arabinoside tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster V79 cells at Covance Laboratories, Harrogate, UK in support of OECD draft Test Guideline 487.

PubMed

Whitwell, James; Fowler, Paul; Allars, Sarah; Jenner, Karen; Lloyd, Melvyn; Wood, Debbie; Smith, Katie; Young, Jamie; Jeffrey, Laura; Kirkland, David

2010-10-29

The reference genotoxic agents 5-fluorouracil (a nucleoside analogue, characterised by a steep dose response profile), colchicine (an aneugen that inhibits tubulin polymerisation), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation) and cytosine arabinoside (a nucleoside analogue that inhibits the gap-filling step of excision repair) were tested in the in vitro micronucleus assay using the Chinese hamster V79 cell line at Covance Laboratories, Harrogate, UK. All chemicals were treated in the absence and presence of cytokinesis block (via addition of cytochalasin B) with this work forming part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 on the In Vitro Mammalian Cell Micronucleus Test (MNvit). The toxicity measures used, detecting a possible combination of both cytostasis and cell death (though not cell death directly), were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index in the presence of cytokinesis block. All of the chemicals tested either gave marked increases in the percentage of micronucleated cells with and without cytokinesis block, or did not induce micronuclei at concentrations giving approximately 50-60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcome from this series of tests supports the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

REFINING OF ASTHMA PREVALENCE SPATIAL DISTRIBUTION AND VISUALIZATION OF OUTDOOR ENVIRONMENT FACTORS USING GIS AND ITS APPLICATION FOR IDENTIFICATION OF MUTUAL ASSOCIATIONS.

PubMed

Škarková, Pavla; Kadlubiec, Radek; Fischer, Michal; Kratěnová, Jana; Zapletal, Miloš; Vrubel, Jiři

2015-09-01

This study presents a procedure of complex assessment of the environment impact on asthma prevalence. This approach is also applicable for any other disease which is supposed to be associated with the quality of the outdoor environment. The input data included asthma prevalence values from the National Institute of Public Health (NIPH) cross-section questionnaire survey (13,456 children) and annual reports on activities of all paediatricians in the Czech Republic (2,072 surgeries); concentrations of PM10, PM2.5, NO2, SO2, O3, benzene, benzo(a)pyrene, As, Cd, Pb and Ni; emissions of total suspended particles, SO2, NOx, CO, VOC, NH3; traffic intensity; land cover (anthropogenic area, urban greenery, arable land, grassland, other agricultural land, forests); proportion of cultivation of individual agricultural crops (17 categories); and proportion of individual woods (15 categories). Using the Geographical Information Systems (GIS) analysis the integration of all source data through one spatial unit was achieved and complete data sets were compiled to be subjected to statistical analysis (combination of factor analysis with logistic/linear regression). In this study, the approach of combined use of GIS analyses and statistical evaluation of large input data sets was tested. The asthma prevalence demonstrated positive associations with the air pollution (PM10, PM2.5, benzene, benzo(a)pyren, SO2, Pb, Cd) and the rate of agricultural use of land (growing oats, rye, arable fodder crops). Conversely, there was a negative association with the occurrence of natural forests (ash, poplar, fir, beech, spruce, pine). No significant associations were observed with the distance from the road, traffic intensity and NO2 concentration. These findings suggest that the outdoor quality may be one of the crucial factors for asthma prevalence.

PAH Particles Perturb Prenatal Processes and Phenotypes: Protection from Deficits in Object Discrimination Afforded by Dampening of Brain Oxidoreductase Following In Utero Exposure to Inhaled Benzo(a)pyrene

PubMed Central

Chadalapaka, Gayathri; Ramesh, Aramandla; Khoshbouei, Habibeh; Maguire, Mark; Safe, Stephen; Rhoades, Raina E.; Clark, Ryan; Jules, George; McCallister, Monique; Aschner, Michael; Hood, Darryl B.

2012-01-01

The wild-type (WT) Cprlox/lox (cytochrome P450 oxidoreductase, Cpr) mouse is an ideal model to assess the contribution of P450 enzymes to the metabolic activation and disposition of environmental xenobiotics. In the present study, we examined the effect of in utero exposure to benzo(a)pyrene [B(a)P] aerosol on Sp4 and N-methyl-D-aspartate (NMDA)–dependent systems as well as a resulting behavioral phenotype (object discrimination) in Cpr offspring. Results from in utero exposure of WT Cprlox/lox mice were compared with in utero exposed brain-Cpr-null offspring mice. Null mice were used as they do not express brain cytochrome P4501B1–associated NADPH oxidoreductase (CYP1B1-associated NADPH oxidoreductase), thus reducing their capacity to produce neural B(a)P metabolites. Subsequent to in utero (E14–E17) exposure to B(a)P (100 μg/m3), Cprlox/lox offspring exhibited: (1) elevated B(a)P metabolite and F2-isoprostane neocortical tissue burdens, (2) elevated concentrations of cortical glutamate, (3) premature developmental expression of Sp4, (4) decreased subunit ratios of NR2B:NR2A, and (5) deficits in a novelty discrimination phenotype monitored to in utero exposed brain-Cpr-null offspring. Collectively, these findings suggest that in situ generation of metabolites by CYP1B1-associated NADPH oxidoreductase promotes negative effects on NMDA-mediated signaling processes during the period when synapses are first forming as well as effects on a subsequent behavioral phenotype. PMID:21987461

Sub-acute administration of benzo[a]pyrene (B[a]P) reduces anxiety-related behaviour in adult mice and modulates regional expression of N-methyl-D-aspartate (NMDA) receptors genes in relevant brain regions.

PubMed

Grova, Nathalie; Schroeder, Henri; Farinelle, Sophie; Prodhomme, Emmanuel; Valley, Anne; Muller, Claude P

2008-08-01

Abnormal glutamatergic transmission caused by modulation of N-methyl-D-aspartate (NMDA) receptors was demonstrated in animal models chronically exposed to various organic micropollutants. Recent developments in neurobiology have implicated these receptors in the regulation of anxiety. In order to investigate anxiety-related effects of benzo[a]pyrene (B[a]P), Balb/c mice were sub-acutely exposed to B[a]P (0.02-200 mg kg(-1) day(-1), 10 days, i.p.). Their performance was tested in the elevated-plus maze and the hole-board apparatus and the NMDA receptor expression genes (NR1, 2A and 2B subunits) was measured in eight brain regions. Mice treated with 20-200 mg kg(-1) B[a]P showed a disproportionate accumulation of B[a]P and its metabolites (in particular, the toxic 7,8-diol-B[a]P) in the blood and even more in the brain. These mice were less anxious than controls in the hole-board test and the elevated-plus maze. This observation was associated with an overexpression of the NMDA NR1 receptor gene and concomitant decreases of the NR2A and NR2B subunits expression in the hippocampus, the hypothalamus and the cerebellum. In the temporal cortex, a significant dose-related decrease of NR2A was observed whereas the other subunits remained unchanged. In conclusion, a sub-acute exposure to B[a]P (20 and 200 mg kg(-1)) reduced anxiety-related behaviour in adult mice and concomitantly impaired NMDA receptor gene expression in relevant brain regions.

PAH determination based on a rapid and novel gas purge-microsyringe extraction (GP-MSE) technique in road dust of Shanghai, China: Characterization, source apportionment, and health risk assessment.

PubMed

Zheng, Xin; Yang, Yi; Liu, Min; Yu, Yingpeng; Zhou, John L; Li, Donghao

2016-07-01

A novel cleanup technique termed as gas purge-microsyringe extraction (GP-MSE) was evaluated and applied for polycyclic aromatic hydrocarbon (PAH) determination in road dust samples. A total of 68 road dust samples covering almost the entire Shanghai area were analyzed for 16 priority PAHs using gas chromatography-mass spectrometry. The results indicate that the total PAH concentrations over the investigated sites ranged from 1.04μg/g to 134.02μg/g dw with an average of 13.84μg/g. High-molecular-weight compounds (4-6 rings PAHs) were significantly dominant in the total mass of PAHs, and accounted for 77.85% to 93.62%. Diagnostic ratio analysis showed that the road dust PAHs were mainly from the mixture of petroleum and biomass/coal combustions. Principal component analysis in conjunction with multiple linear regression indicated that the two major origins of road dust PAHs were vehicular emissions and biomass/fossil fuel combustions, which contributed 66.7% and 18.8% to the total road dust PAH burden, respectively. The concentration of benzo[a]pyrene equivalent (BaPeq) varied from 0.16μg/g to 24.47μg/g. The six highly carcinogenic PAH species (benz(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, benzo(k)fluoranthene, dibenz(a,h)anthracene, and indeno(1,2,3-cd)pyrene) accounted for 98.57% of the total BaPeq concentration. Thus, the toxicity of PAHs in road dust was highly associated with high-molecular-weight compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

PubMed

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

Disturbance of Bcl-2, Bax, Caspase-3, Ki-67 and C-myc expression in acute and subchronic exposure to benzo(a)pyrene in cervix.

PubMed

Gao, Meili; Li, Yongfei; Ji, Xiaoying; Xue, Xiaochang; Chen, Lan; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Shah, Walayat; Hou, Zhanwu; Kong, Yu

2016-03-01

Epidemiological studies have demonstrated that cigarette smoking is an important cofactor or an independent risk factor for the development of cervical cancer. Benzo(a)pyrene (BaP) is one of the most potent tobacco smoke carcinogens in tobacco smoke. BaP induced DNA damage and over expression in p53 cervical tissue of mice as demonstrated in our previous study. Here we present the findings of exposure to BaP on the expression of Bcl-2, C-myc, Ki-67, Caspase-3 and Bax genes in mouse cervix. Acute intraperitoneal administration of BaP (12.5, 25, 50, 100mg/kg body weight) to ICR female mice induced a significant increase in Bcl-2, C-myc, Ki-67 mRNA and protein level till 72h except in Bcl-2 at 24h with 12.5, 25, 50mg/kg as well as at 48h with 12.5mg/kg body weight post treatment. A significant increase was also seen in Caspase-3 and Bax mRNA and protein level with peak level at 24h and gradual decrease till 72h, however, the expression of caspase-3 increased while that of Bax decreased with increasing dose of Bap after 24h. In sub chronic intraperitoneal and oral gavage administration of BaP (2.5, 5, 10mg/kg body weight), similar significant increase was observed for all the examined genes as compared to the control and vehicle groups, however the expression of Bax decreased in a dose dependent manner. The findings of this study will help in further understanding the molecular mechanism of BaP induced carcinogenesis of cervical cancer. Copyright © 2015 Elsevier GmbH. All rights reserved.

Xeroderma pigmentosum, complementation group D expression in H1299 lung cancer cells following benzo[a]pyrene exposure as well as in head and neck cancer patients.

PubMed

Lin, Chang-Shen; Chiou, Wen-Yen; Lee, Ka-Wo; Chen, Tzu-Fen; Lin, Yuan-Jen; Huang, Jau-Ling

2016-01-01

DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers' cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival.

Cytochrome P450 system expression and DNA adduct formation in the liver of Zacco platypus following waterborne benzo(a)pyrene exposure: implications for biomarker determination.

PubMed

Lee, Jin Wuk; Kim, Yong Hwa; Yoon, Seokjoo; Lee, Sung Kyu

2014-09-01

Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon that causes mutations and tumor formation. Zacco platypus is a sentinel species that is suitable for monitoring aquatic environments. We studied cytochrome P450 system (CYP system) expression and DNA adduct formation in the liver of Z. platypus following waterborne exposure to BaP. The results showed both dose and time dependency. The significant induction levels of CYP system mRNA and protein reached maximums at 2 days and 14 days, respectively, and hepatosomatic index was maximally induced at 4 days during 14 days BaP exposure. DNA adduct formation was significantly induced compared to corresponding controls (t-test, p < 0.01) after 4 days of exposure in 100 μg/L BaP. These results indicate that the only use of mRNA expression level of CYP system as a biomarker make us underestimate prolonged toxicity (4-14 days) of BaP and the only use of protein expression level of CYP system make us underestimate acute toxicity (1-2 days) of BaP. Therefore, we suggests that a combinational use of the mRNA expression level and protein expression level of CYP system, hepatosomatic index is a useful biomarker in risk assessment of waterborne BaP exposure. In addition, DNA adduct formation was a useful biomarker in risk assessment of waterborne BaP exposure at 4 days. CYP1A was a more sensitive biomarker than CYP reductase for BaP exposure when considering both the mRNA and protein level. Furthermore, our results show that Z. platypus is a useful species for assessing the risk of waterborne BaP exposure. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Toxicogenomic analysis in the combined effect of tributyltin and benzo[a]pyrene on the development of zebrafish embryos.

PubMed

Huang, Lixing; Zuo, Zhenghong; Zhang, Youyu; Wang, Chonggang

2015-01-01

There is a growing recognition that the toxic effects of chemical mixtures are been an important issue in toxicological sciences. Tributyltin (TBT) and benzo[a]pyrene (BaP) are widespread pollutants that occur simultaneously in the aquatic environments. This study was designed to examine comprehensively the combined effects of TBT and BaP on zebrafish (Danio rerio) embryos using toxicogenomic approach combined with biochemical detection and morphological analysis, and tried to gain insight into the mechanisms underlying the combined effects of TBT and BaP. The results of toxicogenomic data indicated that: (1) TBT cotreatment rescued the embryos from decreased hatching ratio caused by BaP alone, while the alteration of gene expression (in this article the phrase gene expression is used as a synonym to gene transcription, although in is acknowledged that gene expression can also be regulated by, e.g., translation and mRNA or protein stability) relative to zebrafish hatching in the BaP groups was resumed by the cotreatment with TBT; (2) BaP cotreatment decreased TBT-mediated dorsal curvature, and alleviated the perturbation of Notch pathway caused by TBT alone; (3) cotreatment with TBT decreased BaP-mediated bradycardia, which might be due to that TBT cotreatment alleviated the perturbation in expression of genes related to cardiac muscle cell development and calcium handling caused by BaP alone; 4) TBT cotreatment brought an antagonistic effect on the BaP-mediated oxidative stress and DNA damage. These results suggested that toxicogenomic approach was available for analyzing combined toxicity with high sensitivity and accuracy, which might improve our understanding and predictability for the combined effects of chemicals. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of tributyltin and benzo[a]pyrene on the immune-associated activities of hemocytes and recovery responses in the gastropod abalone, Haliotis diversicolor.

PubMed

Gopalakrishnan, Singaram; Huang, Wei-Bin; Wang, Qiang-Wei; Wu, Man-Li; Liu, Jie; Wang, Ke-Jian

2011-08-01

Our previous study reports that short-term exposure to sublethal concentrations of benzo[a]pyrene (BaP) induces immunomodulation in the gastropod abalone, Haliotis diversicolor. In the present study, it was further observed that long-term chronic exposure to sublethal concentrations of BaP modulated the immunocompetence of abalones in terms of the change in activity of the antioxidant and immune associated parameters tested. In addition, the effect of tributyltin (TBT), another important genotoxicant in the aquatic environment, was investigated. Exposure of abalones to sublethal concentrations of TBT and BaP for 21 days resulted in significant decrease of total hemocyte count, phagocytosis, membrane stability and lysozyme activity. Conversely induction of extra and intra cellular superoxide generation, nitric oxide, nitric oxide synthase and myeloperoxidase activity was present when the abalones were exposed to TBT and BaP. Most of the immune associated parameters tested showed clear time dependent response to both toxicants. Within 14 days after the 21 day exposure to BaP, recovery was observed as evidenced by most of the parameters returning to their normal level. However, no recovery was observed within 14 days after the 21 day exposure to TBT as evidenced by continued elevation of intra cellular superoxide and nitrite production and decrease in THC, membrane stability and lysozyme activity. This suggested a prolonged TBT-induced impact on the immune reaction and possibly more damage than that caused by BaP. Overall the results suggest that chronic exposure to sublethal concentrations of TBT or BaP causes modulations in the immunocompetence of abalones with most of the immune associated parameters tested being stimulated, and this might be harmful to the host. Copyright © 2011 Elsevier Inc. All rights reserved.

Bioavailability and biotransformation of benzo(a)pyrene in an isolated perfused In situ catfish intestinal preparation.

PubMed Central

Kleinow, K M; James, M O; Tong, Z; Venugopalan, C S

1998-01-01

In the aquatic environment, diet is an important route of exposure for the common contaminant and procarcinogen benzo(a)pyrene (BaP). Dietary organisms vary in their BaP content and in contaminated areas often contain other xenobiotics including cytochrome P4501A inducers. This study examined the effect of dose and previous dietary exposure to the inducer ss-naphthoflavone (BNF) upon the intestinal metabolism of BaP and the systemic bioavailability of BaP-derived products in catfish. BaP was administered at 2 and 20 microM into in situ-isolated perfused intestines of control and BNF-pretreated catfish. The intestine formed an array of metabolites in all treatments including potentially hazardous metabolites such as BaP-7,8 and 9,10 dihydrodiols and 6-methyl-BaP. BNF treatment disproportionally increased the contribution of BaP-7,8 and 9,10 dihydrodiols relative to the contributions of other metabolites. A greater percentage of metabolites was evident as conjugates in 2 microM controls, whereas a greater percentage of unconjugated metabolites was evident for 20 microM controls and BNF treatments of both dosages. BNF pretreatment and the higher 20 microM BaP dosage resulted in greater bioavailability, with 2.6-5.5-fold and 3.0-6. 3-fold increases in systemically available BaP products, respectively. Metabolites represented 10.2-23.1% of the increased bioavailability with BNF treatment, suggesting that mechanisms, in addition to induced metabolism, may be operative. These results indicate that intestinal bioavailability, level of biotransformation, and the metabolic profile of BaP-derived products entering the blood from the intestine may be altered by dose and dietary BNF pretreatment. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9449680

Chemopreventive effect of chrysin, a dietary flavone against benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.

PubMed

Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Barua, Chandan C; Madhana, Rajaram Mohanrao; Dahiya, Vicky; Budhani, Mukesh Kumar; Mallugari, Ramana Reddy; Maramreddy, Suseela Reddy; Gogoi, Ranadeep

2016-04-01

Chemoprevention is considered as one of the most promising and realistic approaches in the prevention of lung cancer. Chrysin, a naturally occurring dietary flavone widely found in Passiflora family of plants and honey, has been studied extensively for its chemopreventive properties. The objective of present study is to divulge the chemopreventive role of chrysin against benzo(a)pyrene [B(a)P] induced lung carcinogenesis in Swiss albino mice. B(a)P was administered orally (50mg/kg body weight) twice a week for four weeks to induce lung cancer in mice. The body weight, lung weight, tumor incidence, lipid peroxidation, carcinoembryonic antigen, enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase) and non-enzymatic antioxidants (reduced glutathione, vitamin E and vitamin C) were estimated. Further, histopathological analysis of lung tissue and western blotting analysis of PCNA, COX-2 and NF-κB were also carried out. Administration of B(a)P resulted in increased lipid peroxides and carcinoembryonic antigen with concomitant decrease in the levels of both enzymatic antioxidants and non-enzymatic antioxidants. Chrysin treatment (250mg/kg body weight) significantly attenuated all these changes thereby showing potent anti lung cancer effect. Further, the anticancer effect of chrysin was confirmed by histopathology of lungs, and immunoblotting analysis of PCNA, COX-2 and NF-κB, where chrysin supplementation downregulated the expression of these proteins and maintained cellular homeostasis. Overall, these findings confirm the chemopreventive potential of chrysin against B(a)P induced lung cancer in Swiss albino mice. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

The multi-functional roles of GNMT in toxicology and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yen, Chia-Hung; Lin, Yu-Ting; Chen, Heng-Li

Although glycine N-methyltransferase (GNMT) has been discovered for five decades, its function was not elucidated until recently. In this review, we discuss the multiple roles of GNMT in toxicology and cancer. Besides catalyzing the production of methylglycine (sarcosine) in one carbon metabolism pathway, GNMT was found to be able to bind a number of polycyclic aromatic hydrocarbons and inhibit DNA adducts formation. Moreover, GNMT exerts protective effects against the cytotoxicity and carcinogenicity of benzo(a)pyrene and aflatoxin B{sub 1} in vitro and in vivo. Occupational study showed that workers who had genotypes with higher GNMT promoter activity may have lower contentmore » of oxidative damaged DNA products in their urine. In terms of cancer, recent studies using GNMT knockout mouse models demonstrated that GNMT deficiency has high penetrance in inducing the development of steatohepatitis and hepatocellular carcinoma. In terms of the mechanism, besides dysregulation of epigenetic modification, insights have been provided by recent identification of two novel proteins interacting with GNMT-DEPTOR and NPC2. These studies suggest that GNMT not only is involved in mTOR signaling pathway, but also plays an important role in the intracellular trafficking of cholesterol. The implication of these findings to the preventive medicine and translational research will be discussed. -- Highlights: ► We discuss the critical roles of GNMT in toxicology and cancer biology. ► GNMT binds benzo(a)pyrene and aflatoxin and inhibits their DNA adduct formation. ► GNMT deficiency is related to liver tumorigenesis both in mice and human. ► GNMT deficiency results in epigenetic dysregulation and metabolic diseases. ► GNMT is involved in mTOR pathway and intracellular trafficking of cholesterol.« less

The polycyclic aromatic hydrocarbons benzo[a]pyrene and phenanthrene inhibit intestinal lipase activity in rainbow trout (Oncorhynchus mykiss).

PubMed

de Gelder, Stefan; Sæle, Øystein; de Veen, Bas T H; Vos, Joëlle; Flik, Gert; Berntssen, Marc H G; Klaren, Peter H M

2017-08-01

Elevated levels of polycyclic aromatic hydrocarbons (PAHs) are detected in aquafeeds where fish oils are (partially) replaced by vegetable oils. The highly lipophilic PAHs solubilize readily in oil droplets and micelles in the intestinal lumen that can affect enzymatic lipid digestion by altering lipase activity. We therefore investigated the effect of two PAHs, benzo[a]pyrene (BaP) and phenanthrene (PHE), on bile salt-activated lipase (BAL) activity in desalted luminal extracts of the proximal intestine of rainbow trout (Oncorhynchus mykiss) using the triacylglycerides rapeseed oil and fish oil as substrates. The hydrolysis of rapeseed oil and fish oil measured at a calculated substrate concentration of 2.2mM, increased linearly up to 30min at 15°C. Substrate dependency under initial velocity conditions was described by simple Michaelis-Menten kinetics with a K m value of 1.2mM for rapeseed and fish oil. Rapeseed oil hydrolysis was inhibited by 1nM BaP and 10nM PHE. The hydrolysis of fish oil was only inhibited by 10μM BaP. The in vitro lipase activity data were corroborated by TLC/HPLC analysis of the reaction products, showing that in the presence of BaP and PHE, 46-80% less free fatty acids (FFA) were hydrolysed from rapeseed and fish oil triacylglycerides. The presence of low concentrations of BaP and PHE decreased rapeseed oil hydrolysis by BAL whereas fish oil hydrolysis was not affected. The replacement of fish oil by rapeseed oil in aquafeeds introduces PAHs that could affect lipid digestion. Copyright © 2017 Elsevier Inc. All rights reserved.

The development of GADD45α luciferase reporter assays in human cells for assessing the genotoxicity of environmental pollutants.

PubMed

Xin, Lili; Wang, Jianshu; Wu, Yanhu; Guo, Sifan

2015-02-01

In order to assess the potential carcinogenic and genotoxic responses induced by environmental pollutants, genotoxicity test systems based on a GADD45α promoter-driven luciferase reporter in human A549 and HepG2 cells were established. Four different types of environmental toxicants including DNA alkylating agents, precarcinogenic agents, DNA cross-linking agents and non-carcinogenic agents, and three environmental samples collected from a coke oven plant were used to evaluate the test systems. After treated with the tested agents and environmental samples for 12 h, the cell viabilities and luciferase activities of the luciferase reporter cells were determined, respectively. Methyl methanesulfonate, benzo[a]pyrene, formaldehyde and the extractable organic matter (EOM) from coke oven emissions in ambient air generally produced significant induction of relative luciferase activity in a similar dose-dependent manner in A549- and HepG2-luciferase cells. No significant increases in relative luciferase activity were observed in pyrene-treated A549- or HepG2-luciferase cells. Significant increase in relative luciferase activity was already evident after 2.5 µM benzo[a]pyrene, 5 µM formaldehyde, 0.006 µg/L bottom-EOM, 0.10 µg/L side-EOM or 0.06 µg/L top-EOM, where no cytotoxic damage was observed. Compared with the A549-luciferase cells, the tested pollutants produced higher induction of relative luciferase activity in HepG2-luciferase cells. Therefore, the new genotoxicity test systems can detect different types of genotoxic agents and low concentrations of environmental samples. The luciferase reporter cells, especially the HepG2-luciferase cells, could provide a valuable tool for rapid screening of the genotoxic damage of environmental pollutants and their complex mixtures.

Experimental exposure of blue mussels (Mytilus galloprovincialis) to high levels of benzo[a]pyrene and possible implications for human health.

PubMed

Speciale, A; Zena, R; Calabrò, C; Bertuccio, C; Aragona, M; Saija, A; Trombetta, D; Cimino, F; Lo Cascio, P

2018-04-15

Polycyclic aromatic hydrocarbons (PAHs) are lipophilic compounds able to accumulate in the food chain. Mussels showed to bioaccumulate contaminants, such as PAHs, so that recurrent consumption of such contaminated food represents a risk for human health. This study was aimed to elucidate if acute exposure of Mediterranean blue mussel (Mytilus galloprovincialis), a bivalve of great economic importance in several countries, to a PAH, benzo[a]pyrene (B[a]P), at doses able to induce cytochrome P450 1A (CYP1A) and pathological changes in mussel gills, can produce accumulation in soft tissue. We explored the cytotoxic effects (cell viability, DNA laddering, and glutathione levels) of in vitro exposure of human peripheral blood mononuclear cells (PBMCs) to organic extracts obtained from blue mussels previously exposed for 12 and 72h via water to B[a]P (0.5-1mg/L). In our experimental conditions, B[a]P induced CYP1A induction and morphological changes in mussel gills and a significant B[a]P accumulation in soft tissue. Conversely, exposing PBMCs to organic extracts obtained from contaminated mussels, resulted in a significant reduction of cell viability and cell glutathione content, and in an increase in DNA laddering. This confirms that consumption of mussels from B[a]P polluted waters might affect human health. Our data lead us to suggest that CYP1A activity in mussel gills may be useful (more than the amount of detected PAHs in the mussel edible tissue) as a marker in assessment of risk for health of consumers exposed to PAHs through ingestion of shellfish. Copyright © 2017 Elsevier Inc. All rights reserved.

Analysis of fish bile with HPLC — fluorescence to determine environmental exposure to benzo(a)pyrene

USGS Publications Warehouse

Johnston, Eric P.; Baumann, Paul C.

1989-01-01

Brown bullhead from the Black River, Ohio, have a high incidence of liver neoplasia which is associated with elevated concentrations of polynuclear aromatic hydrocarbons (PAHs) in the sediment. We evaluated the use of biliary concentrations of benzo(a)pyrene [B(a)P] equivalents as a means for determining PAH exposure. Bile was collected from 16 brown bullheads and 8 common carp taken from each of two Lake Erie tributaries in Ohio, the industrialized Black River and the non-industrialized Old Woman Creek. Hatchery bullhead (n = 8) were used to determine base levels of PAHs. A high performance liquid chromatography (HPLC) — fluorescence technique was used to determine the concentration of B(a)P equivalents in the bile samples. The area of all peaks fluorescing at 380/430 nm was summed to give a single value for B(a)P equivalents in each sample. Concentrations of B(a)P equivalents generally reflected concentrations of PAH in sediment where fish were collected. Bile taken from Black River carp contained the highest concentration of B(a)P equivalents and was significantly different from all other groups. The value obtained for Black River bullhead was also high and was found to be significantly different from hatchery bullhead. B(a)P equivalents varied between carp and bullhead from the same habitat possibly because of differing food habits or metabolic pathways. However, our results indicate that relative levels of B(a)P equivalents in the bile of fish correspond well to B(a)P levels in sediment and may offer a means of determining environmental exposure of fish to the parent compound.

Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie

Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2 mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured inmore » 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. - Highlights: • B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions. • B[a]P had measurable consequences on anxiety, short term learning and memory. • B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P. • Vaccination may also provide some protection against chemical carcinogenesis.« less

Subchronic exposure of benzo(a)pyrene interferes with the expression of Bcl-2, Ki-67, C-myc and p53, Bax, Caspase-3 in sub-regions of cerebral cortex and hippocampus.

PubMed

He, Jianlong; Ji, Xiaoying; Li, Yongfei; Xue, Xiaochang; Feng, Guodong; Zhang, Huqin; Wang, Huichun; Gao, Meilii

2016-01-01

Benzo[a]pyrene [B(a)P], a representative substance of the polycyclic aromatic hydrocarbons, is an ubiquitous environmental contaminant. However, the mechanism of B(a)P neurotoxicity is still not clear. The aim of this study was to investigate the molecular mechanism by assay the expression of Bcl-2, C-myc, Ki-67 oncogene and p53, Bax, Caspase-3 proapoptotic gene in sub-regions of cerebral cortex and hippocampus in brain. Mice were administrated with subchronic intraperitoneal injection and oral gavage of B(a)P (2.5, 5, 10mg/kg body weight) for 13 weeks. We observed that B(a)P induced the significant increase in relative brain weights and the slight proliferation phenomenon in hippocampus in the experiment. Significant increase of C-myc, Ki-67 and p53, Bax, Caspase-3 and dramatic decrease of Bcl-2 protein levels were observed through immunohistochemical analysis. The relative higher interference of Bcl-2, C-myc, Ki-67 and p53, Bax, Caspase-3 proteins was observed in hippocampus sub-regions of dentate gyrus, cornu ammonis 3 and cornu ammonis 1. The relative lower interference of the examined genes was found in cerebral cortex sub-regions of frontal cortex, temporal cortex and parietal cortex. The results showed a region-difference manner with accompanying dose-dependent manner in brain hippocampus and cerebral cortex induced by B(a)P. These findings indicate that B(a)P-induced subchronic neural toxicity may occur through the enhancement in Bcl-2, C-myc, Ki-67 oncogenes and p53, Bax, Caspase-3 proapoptotic genes expression. Copyright © 2015 Elsevier GmbH. All rights reserved.

Polycyclic aromatic hydrocarbons in Cambodian smoked fish.

PubMed

Slámová, Tereza; Fraňková, Adéla; Hubáčková, Anna; Banout, Jan

2017-12-01

More than 85% of the population in Cambodia is strongly dependent on agriculture, of which freshwater aquaculture is one of the most important sources of food production. The smoked fish represents an important source of nutrients for Cambodian population; however, it can also lead to excessive intake of polycyclic aromatic hydrocarbons (PAHs). A field survey was conducted among selected smoked fish producers near to Tonle Sap river in Kampong Chhnang province, Cambodia. The study revealed that maximal limits for benzo[a]pyrene and the sum of four PAHs given by EC 1881/2006 were exceeded 2-50 times. Such burden can lead to increased risk of development of carcinogenic diseases.

Residential Segregation, Housing Status, and Prostate Cancer in African American and White Men

DTIC Science & Technology

2008-04-01

and Leu432Val, microsomal epoxide hydrolase (mEH) Tyr113His and His139Arg, CYP3A4 A(−392)G] and conjugation [glutathione S-transferase (GST) M1 null...CYP1B1, or CYP3A4 (16) can then transform the dihydrodiol to a highly reactive diol-epoxide [benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide, BPDE] that can...Although mEH (18) and CYP1B1 (19) are expressed in the prostate, CYP1A1 may only be induced under androgen dependency (20) and CYP3A4 may require

Comparison of the genotoxic activities of the K-region dihydrodiol of benzo[a]pyrene with benzo[a]pyrene in mammalian cells: morphological cell transformation; DNA damage; and stable covalent DNA adducts.

PubMed

Nesnow, Stephen; Davis, Christine; Nelson, Garret B; Lambert, Guy; Padgett, William; Pimentel, Maria; Tennant, Alan H; Kligerman, Andrew D; Ross, Jeffrey A

2002-11-26

Benzo[a]pyrene (B[a]P) is the most thoroughly studied polycyclic aromatic hydrocarbon (PAH). Many mechanisms have been suggested to explain its carcinogenic activity, yet many questions still remain. K-region dihydrodiols of PAHs are metabolic intermediates depending on the specific cytochrome P450 and had been thought to be detoxification products. However, K-region dihydrodiols of several PAHs have recently been shown to morphologically transform mouse embryo C3H10T1/2CL8 cells (C3H10T1/2 cells). Because K-region dihydrodiols are not metabolically formed from PAHs by C3H10T1/2 cells, these cells provide a useful tool to independently study the mechanisms of action of PAHs and their K-region dihydrodiols. Here, we compare the morphological cell transforming, DNA damaging, and DNA adducting activities of the K-region dihydrodiol of B[a]P, trans-B[a]P-4,5-diol with B[a]P. Both trans-B[a]P-4,5-diol and B[a]P morphologically transformed C3H10T1/2 cells by producing both Types II and III transformed foci. The morphological cell transforming and cytotoxicity dose response curves for trans-B[a]P-4,5-diol and B[a]P were indistinguishable. Since morphological cell transformation is strongly associated with mutation and/or larger scale DNA damage in C3H10T1/2 cells, the identification of DNA damage induced in these cells by trans-B[a]P-4,5-diol was sought. Both trans-B[a]P-4,5-diol and B[a]P exhibited significant DNA damaging activity without significant concurrent cytotoxicity using the comet assay, but with different dose responses and comet tail distributions. DNA adduct patterns from C3H10T1/2 cells were examined after trans-B[a]P-4,5-diol or B[a]P treatment using 32P-postlabeling techniques and improved TLC elution systems designed to separate polar DNA adducts. While B[a]P treatment produced one major DNA adduct identified as anti-trans-B[a]P-7,8-diol-9,10-epoxide-deoxyguanosine, no stable covalent DNA adducts were detected in the DNA of trans-B[a]P-4,5-diol-treated cells. In summary, this study provides evidence for the DNA damaging and morphological cell transforming activities of the K-region dihydrodiol of B[a]P, in the absence of covalent stable DNA adducts. While trans-B[a]P-4,5-diol and B[a]P both induce morphological cell transformation, their activities as DNA damaging agents differ, both qualitatively and quantitatively. In concert with the morphological cell transformation activities of other K-region dihydrodiols of PAHs, these data suggest a new mechanism/pathway for the morphological cell transforming activities of B[a]P and its metabolites.

Seasonal Trend of PAHs Concentrations in Farmed Mussels from the Coastal Areas of the Naples, Italy.

PubMed

Esposito, Mauro; Perugini, Monia; Lambiase, Sara; Conte, Annamaria; Baldi, Loredana; Amorena, Michele

2017-09-01

This paper reports on the results about the chemical pollution pressure in the Gulf of Naples and nearby coastal areas. Farmed mussels were analysed for the presence of polycyclic aromatic hydrocarbons (PAHs). The results documented a decreasing trend in the PAHs levels respect to the past years. The Bay of Pozzuoli remains as the most contaminated site within the Lucrino area with the highest reported number of samples exceeding the benzo(a)pyrene and PAHs sum limits. All the samples with concentrations above the European regulatory limit were collected in the winter period illustrating a seasonal trend of PAHs distribution in mussels during the 4 years investigated.

In Vitro Chemical Carcinogenesis and Co-Carcino-genesis in Human Cells Initiated by Hydrazine and Polynuclear Components of Jet Fuel

DTIC Science & Technology

1980-09-01

cats exposed to methylnitrosourea, Cancer Res., 38, 996, 1978. 12. Prehn, R.T’, Function of depressed immunologic reactivity during carcinogenesis, 3...4/8 UDH 50.0 N.D. 5.1 4/8 MAMA 3.6 N.D. 900.0 2/16 B(a)P 10.0 39 1.0 6/10 MMS 0.1 2500 0 0/6 U.V. 40 J.m-2 78 20.0 4/6 137Cs 100 r 39 13.1 3/7...intracellular distribution and binding of benzo(a)pyrene in human dysloid fibroblasts. Cancer Letters 10:57-65. 2. G. Milo, G.A. Ackerman, and I

Continuous human cell lines and method of making same

DOEpatents

Stampfer, Martha R.

1989-01-01

Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo[a]pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors.

In vitro protective effects of botryosphaeran, a (1→3;1→6)-β-d-glucan, against mutagens in normal and tumor rodent cells.

PubMed

Kerche-Silva, Leandra E; Cólus, Ilce M S; Malini, Maressa; Mori, Mateus Prates; Dekker, Robert F H; Barbosa-Dekker, Aneli M

2017-02-01

Botryosphaeran (BOT) is an exocellular β-d-glucan (carbohydrate biopolymer) of the (1→3;1→6)-linked type produced by Botryosphaeria rhodina MAMB-05. The cytotoxic, mutagenic, genotoxic, and protective effects of this substance were evaluated in Chinese hamster lung fibroblasts (V79) and rat hepatocarcinoma cells (HTC) by the micronucleus test (MN) and the comet assay. BOT was not genotoxic in either cell line; it decreased the clastogenic effects of doxorubicin, H 2 O 2 , and benzo[a]pyrene. These results indicate that BOT may have potential as a therapeutic agent. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomonitoring of Air Condition in Urban Environment (with Regard to Irkutsk, Irkutsk region in Russia)

NASA Astrophysics Data System (ADS)

Belykh, L. I.

2017-11-01

The paper deals with the results of investigation into the contents and distribution of cancer-causing benzo(a)pyrene in the leaves of the trees that are common in the urban environment of Irkutsk. The degree of plant pollution is determined depending on the landscape and traffic exposure, on the mode of the plant material being prepared and on its type. The methodology for landscape geochemical biomonitoring is offered to be used at the stages of sample sorting and preparation and in the statistical treatment of the analysis results obtained. The possibility to use tree leaves as biotest materials for the urban atmosphere state control is considered in the paper.

Modified clay sorbents

DOEpatents

Fogler, H. Scott; Srinivasan, Keeran R.

1990-01-01

A novel modified clay sorbent and method of treating industrial effluents to remove trace pollutants, such as dioxins, biphenyls, and polyaromatics such as benzo(a)pyrene and pentachlorophenol. The novel clay sorbent has a composite structure in which the interlayer space of an expandable clay, such as smectite, is filled with polyvalent or multivalent inorganic cations which forces weaker surfactant cations to locate on the surface of the clay in such an orientation that the resulting composite is hydrophilic in nature. A specific example is cetylpyridinium-hydroxy aluminum-montmorillonite. In certain embodiments, a non-expanding clay, such as kaolinite, is used and surfactant cations are necessarily located on an external surface of the clay. A specific example is cetylpyridinium-kaolinite.

Exposure to di(n-butyl)phthalate and benzo(a)pyrene alters IL-1{beta} secretion and subset expression of testicular macrophages, resulting in decreased testosterone production in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng Shanjun; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing 400038; Key Laboratory of High Altitude Physiology and High Altitude Disease, PLA, Chongqing 400038

Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1{beta}), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1{beta} secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plusmore » BaP (DBP + BaP: 50 + 1 or 250 + 5 mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250 mg/kg/day; BaP: 1 or 5 mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90 days, the relative expression of macrophage subsets and their functions changed. ED2{sup +} testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1{beta} secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1{beta} secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1{beta}, resulted in enhanced production of IL-1{beta} as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis.« less

Olive oil prevents benzo(a)pyrene [B(a)P]-induced colon carcinogenesis through altered B(a)P metabolism and decreased oxidative damage in ApcMin mouse model

PubMed Central

Banks, Leah D.; Amoah, Priscilla; Niaz, Mohammad S.; Washington, Mary K.; Adunyah, Samuel E.; Ramesh, Aramandla

2015-01-01

Colon cancer ranks third in cancer related mortalities in the United States. Many studies have investigated factors that contribute to colon cancer in which dietary and environmental factors have been shown to play an integral role in the etiology of this disease. Specifically, human dietary intake of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs) has generated interest in looking at how it exerts its effects in gastrointestinal carcinogenesis. Therefore, the objective of this study was to investigate the preventative effects of olive oil on benzo(a)pyrene [B(a)P]-induced colon carcinogenesis in adult ApcMin mice. Mice were assigned to a control (n =8) or treatment group (n =8) consisting of 25, 50 and 100 μg B(a)P/kg body weight (bw) dissolved in tricaprylin [B(a)P-only group] or olive oil daily via oral gavage for sixty days. Our studies showed that ApcMin mice exposed to B(a)P developed a significantly higher number (p< 0.05) of larger dysplastic adenomas compared to those exposed to B(a)P + olive oil. Treatment of mice with B(a)P and olive oil significantly altered (p< 0.05) the expression of drug metabolizing enzymes in both the colon and liver tissues. However, only GST activity was significantly higher (p< 0.05) in the liver of mice treated with 50 and 100 μg B(a)P/kg bw + olive oil. Lastly, olive oil promoted rapid detoxification of B(a)P by decreasing its organic metabolite concentrations and also decreasing the extent of DNA damage to colon and liver tissues (p< 0.05). These results suggest that olive oil has a protective effect against B(a)P-induced colon tumors. PMID:26878781

Multidrug resistance protein (MRP) 4 attenuates benzo[a]pyrene-mediated DNA-adduct formation in human bronchoalveolar H358 cells.

PubMed

Gelhaus, Stacy L; Gilad, Oren; Hwang, Wei-Ting; Penning, Trevor M; Blair, Ian A

2012-02-25

Multi-drug resistance protein (MRP) 4, an ATP-binding cassette (ABC) transporter, has broad substrate specificity. It facilitates the transport of bile salt conjugates, conjugated steroids, nucleoside analogs, eicosanoids, and cardiovascular drugs. Recent studies in liver carcinoma cells and hepatocytes showed that MRP4 expression is regulated by the aryl hydrocarbon receptor (AhR) and nuclear factor E2-related factor 2 (Nrf2). The AhR has particular importance in the lung and is most commonly associated with the up-regulation of cytochrome P-450 (CYP)-mediated metabolism of benzo[a]pyrene (B[a]P) to reactive intermediates. Treatment of H358, human bronchoalveolar, cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or (-)-benzo[a]pyrene-7,8-dihydro-7,8-diol (B[a]P-7,8-dihydrodiol), the proximate carcinogen of B[a]P, revealed that MRP4 expression was increased compared to control. This suggested that MRP4 expression might contribute to the paradoxical decrease in (+)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-2'-deoxyguanosine ((+)-anti-trans-B[a]PDE-dGuo) DNA-adducts observed in TCDD-treated H358 cells. We have now found that decreased MRP4 expression induced by a short hairpin RNA (shRNA), or chemical inhibition with probenecid, increased (+)-anti-trans-B[a]PDE-dGuo formation in cells treated with (-)-B[a]P-7,8-dihydrodiol, but not the ultimate carcinogen (+)-anti-trans-B[a]PDE. Thus, up-regulation of MRP4 increased cellular efflux of (-)-B[a]P-7,8-dihydrodiol, which attenuated DNA-adduct formation. This is the first report identifying a specific MRP efflux transporter that decreases DNA damage arising from an environmental carcinogen. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Pyrene and benzo[a]pyrene metabolism by the filamentous fungus, Penicillium janthinellum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Launen, L.; Pinto, L.; Kiehlmann, E.

1995-12-31

The incomplete combustion of fossil fuels generates polycyclic aromatic hydrocarbons (PAH). These include 4-5 ring PAH, of which many are potent carcinogens and mutagens that persist in soil for years. Fungi can oxidize these compounds via two mechanisms: (1) by extracellular peroxidases (Basidiomycete fungi), or (2) by a putative cytochrome P450 enzyme system. The authors have previously isolated Penicillium janthinellum from petroleum-contaminated soil and shown that it possesses high activity to oxidize pyrene, benzo(a)pyrene and chrysene in liquid culture. The purpose of this study was to evaluate the effect of changing growth condition glucose, nitrate and agitation levels, on pyrenemore » metabolism by P. janthinellum using a 3 x 2 x 2 factorial design. Spores were inoculated into minimal salts media amended with varying carbon or nitrogen concentrations and containing {sup 14}C-pyrene. The level of glucose and nitrate significantly affected the bioconversion: low glucose and nitrate levels increased the loss of parent PAH from the medium. However this effect was independent of biomass. Biometer flask experiments using {sup 14}C-pyrene showed that most pyrene became cell-associated within 7 days of incubation. Cell associated {sup 14}C-pyrene was inextractable by ethyl acetate but was recovered in methylene chloride. This result was confirmed by the mass balance result from a 10 day time course experiment using {sup 14}C-pyrene or {sup 14}C-BaP. Greater than 70% of the radiolabel in cultures containing live cells was strongly associated with the cell matter within 7 days, relative to < 1 % association with dead cells. The authors conclude that: (1) pyrene and BaP oxidation was affected by C and N levels in the growth medium independent of cell mass and (2) {sup 14}C-PAH became strongly associated with live but not dead cells within 7 days in liquid culture.« less

Usefulness of oxidative stress biomarkers evaluated in the snout scraping, serum and Peripheral Blood Cells of Crocodylus moreletii from Southeast Campeche for assessment of the toxic impact of PAHs, metals and total phenols.

PubMed

Dzul-Caamal, Ricardo; Hernández-López, Abigail; Gonzalez-Jáuregui, Mauricio; Padilla, Sergio E; Girón-Pérez, Manuel Ivan; Vega-López, Armando

2016-10-01

In this study, we assessed the effects of inorganic and organic pollutants [As, Cu, Fe, Mn, Pb, Zn, PAHs (11 compounds) and total phenols] from a panel of biomarkers [O2, H2O2, thiobarbituric acid reactive substances (TBARS), carbonyl proteins (RCO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total cytochrome P450 activities] evaluated in the Snout Scraping (SS), Serum (S) and Peripheral Blood Cells (PBC) of the Morelet's crocodile (Crocodylus moreletii) inhabiting the reference locality (Lake Mocu) and polluted locality (Champoton River) using Principal Component Analysis (PCA). In male crocodiles from the reference site, only H2O2 in PBC was related to levels of fluoranthene on the Keel of Caudal Scales (KCS), but, in females, no association was detected. In contrast, a sex-linked response was detected in specimens from the polluted locality. Levels of benzo[a]pyrene, benzo[a]anthracene, chrysene, pyrene, phenanthrene, acenaphthene, Zn, Cu, and Pb in KCS of the female crocodil were related to the oxidative stress biomarkers on PBC, incluing the total CYP450 activity and levels of O2, H2O2 in serum. However, in male crocodiles, the oxidative stress in SS and in the serum (TBARS, RCO, CAT, GPx), and SOD in PBC was related to As, Pb, Cu, Fe, and benzo[a]pyrene water concentrations and to the burdens of As, Fe, Mn, indeno[1,2,3cd]pyrene in KCS. These results confirm the usefulness of minimal or non-invasive methods of evaluating the oxidative stress response for the environmental monitoring program on the wild Morelet's crocodile that is subject to special protection in Mexican guidelines. Copyright © 2016 Elsevier Inc. All rights reserved.

Circadian Regulation of Benzo[a]Pyrene Metabolism and DNA Adduct Formation in Breast Cells and the Mouse Mammary Gland

PubMed Central

Schmitt, Emily E.; Barhoumi, Rola; Metz, Richard P.

2017-01-01

The circadian clock plays a role in many biologic processes, yet very little is known about its role in metabolism of drugs and carcinogens. The purpose of this study was to define the impact of circadian rhythms on benzo-a-pyrene (BaP) metabolism in the mouse mammary gland and develop a circadian in vitro model for investigating changes in BaP metabolism resulting from cross-talk between the molecular clock and aryl hydrocarbon receptor. Female 129sv mice (12 weeks old) received a single gavage dose of 50 mg/kg BaP at either noon or midnight, and mammary tissues were isolated 4 or 24 hours later. BaP-induced Cyp1a1 and Cyp1b1 mRNA levels were higher 4 hours after dosing at noon than at 4 hours after dosing at midnight, and this corresponded with parallel changes in Per gene expression. In our in vitro model, we dosed MCF10A mammary cells at different times after serum shock to study how time of day shifts drug metabolism in cells. Analysis of CYP1A1 and CYP1B1 gene expression showed the maximum enzyme-induced metabolism response 12 and 20 hours after shock, as determined by ethoxyresorufin-O-deethylase activity, metabolism of BaP, and formation of DNA-BaP adducts. The pattern of PER-, BMAL-, and aryl hydrocarbon receptor–induced P450 gene expression and BaP metabolism was similar to BaP-induced Cyp1A1 and Cyp1B1 and molecular clock gene expression in mouse mammary glands. These studies indicate time-of-day exposure influences BaP metabolism in mouse mammary glands and describe an in vitro model that can be used to investigate the circadian influence on the metabolism of carcinogens. PMID:28007926

Benzo(a)pyrene induced cell cycle arrest and apoptosis in human choriocarcinoma cancer cells through reactive oxygen species-induced endoplasmic reticulum-stress pathway.

PubMed

Kim, Soo-Min; Lee, Hae-Miru; Hwang, Kyung-A; Choi, Kyung-Chul

2017-09-01

Cigarette smoke (CS) contains over 60 well established carcinogens. In this study, we examined the effects of benzo(a)pyrene (B(a)P), a main CS component, on the viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. An MTT assay confirmed that B(a)P decreased the cell viability of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot (WB) assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 was increased in response to B(a)P treatment for 48 h. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to B(a)P were also measured by a dichlorofluorescein diacetate (DCF-DA) assay, which revealed that ROS levels increased in response to B(a)P treatment for 48 h. WB assay also confirmed that each B(a)P treatment of JEG-3 and BeWo cells for 4 h promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α) and C/EBP homologous protein (CHOP), which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress) related apoptosis. Overall, the protein expression of Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to B(a)P treatment for 48 h. Taken together, these results suggest that B(a)P has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by increasing the ROS level and simultaneously activating ER-stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

1-Ethynylpyrene, a suicide inhibitor of cytochrome P-450 dependent benzo(a)pyrene hydroxylase activity in liver microsomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gan, L.S.L.; Acebo, A.L.; Alworth, W.L.

The preparation of 1-ethynylpyrene (EP) by incubation of EP with liver microsomes in the presence of NADPH yields fluorescent products briefly. Addition of microsomes restores the original rate. The metabolism of EP is initially more rapid in microsomes from 5,6-benzoflavone- (BF) pretreated rats than in those from phenobarbital (PB) pretreated rats or controls. Ep inhibits the hydroxylation of benzo(a)pyrene (BP) by liver microsomes. Ep more effectively inhibits the oxidation of BP in liver microsomes from BF rats than from PB rats or from controls. The inhibition of BP hydroxylation activity due to EP is dependent upon NADPH and is apparentlymore » irreversible. Kinetic analyses show that the inhibition of BP hydroxylation is due to loss of the activity by a process that is first order in EP and that reaches a limiting value at infinite EP concentrations. A self-catalyzed inhibition of the cytochrome P-450 dependent BP hydroxylation may occur in the presence of EP. Incubation with EP under conditions that result in loss of BP hydroxylase activity in microsomes from BF rats and 66% of the activity from PB rats causes the loss of 6 and 12% of the cytochrome P-450, respectively. Thus the loss of P-450 content is an insensitive measure of the effect of this inhibitor upon this cytochrome P-450 dependent enzyme activity. Selectivity of the loss of P-450 due to the incubation of the different microsomal preparations with EP is observed to be different than the selectivity for loss of BP hydroxylase activity. It is proposed that the inhibition of cytochrome P-450 dependent enzymes by alkynes need not involve heme alkylation and a resulting loss of P-450 content. In vivo EP does not cause a significant change in the cytochrome P-450 content in the microsomes isolated, or result in the change in BP hydroxylation.« less

Degradation of PAHs in soil by Lasiodiplodia theobromae and enhanced benzo[a]pyrene degradation by the addition of Tween-80.

PubMed

Wang, Cuiping; Liu, Haibin; Li, Jing; Sun, Hongwen

2014-09-01

Benzo[a]pyrene (BaP), a five-ring polycyclic aromatic hydrocarbon (PAH), which has carcinogenic potency, is highly recalcitrant and resistant to microbial degradation. A novel fungus, Lasiodiplodia theobromae (L. theobromae), which can degrade BaP as a sole carbon source in liquid, was isolated in our laboratory. To prompt the further application of L. theobromae in remediation of sites polluted by BaP and other PAHs, the present study was targeted toward the removal of BaP and PAHs from soil by L. theobromae. The degradation of BaP by L. theobromae was studied using a soil spiked with 50 mg/kg BaP. L. theobromae could remove 32.1 % of the BaP after 35 days of cultivation. Phenanthrene (PHE) inhibited BaP degradation as a competitive substrate. The tested surfactants enhanced BaP degradation in soil by different extents, and a removal rate of 92.1 % was achieved at a Tween-80 (TW-80) concentration of 5 g/kg. It was revealed that TW-80 could not only enhance BaP bioavailability by increasing its aqueous solubility and decreasing the size of its colloid particles but also increase enzyme secretion from L. theobromae and the population of L. theobromae. Moreover, ergosterol content together with the biomass C indicated the increase in L. theobromae biomass during the BaP biodegradation process in soils. Finally, a soil from a historically PAH-contaminated field at Beijing Coking Plant in China was tested to assess the feasibility of applying L. theobromae in the remediation of polluted sites. The total removal rate of PAHs by L. theobromae was 53.3 %, which is 13.1 % higher than that by Phanerochaete chrysosporium (P. chrysosporium), an effective PAH degrader. The addition of TW-80 to the field soil further enhanced PAH degradation to 73.2 %. Hence, L. theobromae is a promising novel strain to be implemented in the remediation of soil polluted by PAHs.

Meat, meat cooking methods and preservation, and risk for colorectal adenoma.

PubMed

Sinha, Rashmi; Peters, Ulrike; Cross, Amanda J; Kulldorff, Martin; Weissfeld, Joel L; Pinsky, Paul F; Rothman, Nathaniel; Hayes, Richard B

2005-09-01

Cooking meat at high temperatures produces heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Processed meats contain N-nitroso compounds. Meat intake may increase cancer risk as HCAs, PAHs, and N-nitroso compounds are carcinogenic in animal models. We investigated meat, processed meat, HCAs, and the PAH benzo(a)pyrene and the risk of colorectal adenoma in 3,696 left-sided (descending and sigmoid colon and rectum) adenoma cases and 34,817 endoscopy-negative controls. Dietary intake was assessed using a 137-item food frequency questionnaire, with additional questions on meats and meat cooking practices. The questionnaire was linked to a previously developed database to determine exposure to HCAs and PAHs. Intake of red meat, with known doneness/cooking methods, was associated with an increased risk of adenoma in the descending and sigmoid colon [odds ratio (OR), 1.26; 95% confidence interval (95% CI), 1.05-1.50 comparing extreme quintiles of intake] but not rectal adenoma. Well-done red meat was associated with increased risk of colorectal adenoma (OR, 1.21; 95% CI, 1.06-1.37). Increased risks for adenoma of the descending colon and sigmoid colon were observed for the two HCAs: 2-amino-3,8-dimethylimidazo[4,5]quinoxaline and 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (OR, 1.18; 95% CI, 1.01-1.38 and OR, 1.17, 95% CI, 1.01-1.35, respectively) as well as benzo(a)pyrene (OR, 1.18; 95% CI, 1.02-1.35). Greater intake of bacon and sausage was associated with increased colorectal adenoma risk (OR, 1.14; 95% CI, 1.00-1.30); however, total intake of processed meat was not (OR, 1.04; 95% CI, 0.90-1.19). Our study of screening-detected colorectal adenomas shows that red meat and meat cooked at high temperatures are associated with an increased risk of colorectal adenoma.

Intakes of red meat, processed meat, and meat-mutagens increase lung cancer risk

PubMed Central

Lam, Tram Kim; Cross, Amanda J.; Consonni, Dario; Randi, Giorgia; Bagnardi, Vincenzo; Bertazzi, Pier Alberto; Caporaso, Neil E.; Sinha, Rashmi; Subar, Amy F.; Landi, Maria Teresa

2009-01-01

Red and processed meat intake may increase lung cancer risk. However, the epidemiologic evidence is inconsistent and few studies have evaluated the role of meat-mutagens formed during high cooking temperatures. We investigated the association of red meat, processed meat, and meat-mutagen intake with lung cancer risk in Environment And Genetics in Lung cancer Etiology (EAGLE), a population-based case-control study. Primary lung cancer cases (n=2101) were recruited from 13 hospitals within the Lombardy region of Italy examining ~80% of the cases from the area. Non-cancer population controls (n=2120), matched to cases on gender, residence, and age, were randomly selected from the same catchment area. Diet was assessed in 1903 cases and 2073 controls, and used in conjunction with a meat-mutagen database to estimate intake of heterocyclic amines and benzo[a]pyrene. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific tertiles of intake were calculated using unconditional logistic regression. Red and processed meat were positively associated with lung cancer risk (highest-versus-lowest tertile: OR=1.8; 95% CI=1.5–2.2; p-trend<0.001 and OR=1.7; 95% CI=1.4–2.1; p-trend<0.001, respectively); the risks were strongest among never smokers (OR=2.4, 95% CI=1.4–4.0, p-trend=0.001 and OR=2.5, 95% CI=1.5–4.2, p-trend=0.001, respectively). Heterocyclic amines and benzo[a]pyrene were significantly associated with increased risk of lung cancer. When separated by histology, significant positive associations for both meat groups were restricted to adenocarcinoma and squamous cell carcinoma, but not small cell carcinoma of the lung. In summary, red meat, processed meat, and meat-mutagens were independently associated with increased risk of lung cancer. PMID:19141639

Cytochrome P450 1C1 complementary DNA cloning, sequence analysis and constitutive expression induced by benzo-a-pyrene in Nile tilapia (Oreochromis niloticus).

PubMed

Hassanin, Abeer A I; Kaminishi, Yoshino; Funahashi, Aki; Itakura, Takao

2012-03-01

CYP1C is the newest member of the CYP1 family of P450s; however, its physiological significance, inducers, and metabolic functions are unknown. In this study, a new complementary DNA of the CYP1C subfamily encoding CYP1C1 was isolated from Nile tilapia (Oreochromis niloticus) liver after intracoelomic injection with benzo-a-pyrene (BaP). The full-length cDNA was 2223 base pair (bp) long and contained an open reading frame of 1581 bp encoding a protein of 526 amino acids and a stop codon. The sequence exhibited 3' non-coding region of 642 bp. The deduced amino acid sequence of O. niloticus CYP1C1 shows similarities of 86, 82.5, 79.7, 78.7, 77.8, 75.5, 69.6 and 61.3% with scup CYP1C1, killifish CYP1C1,1C2, Japanese eel CYP1C1, zebra fish CYP1C1, common carp CYP1C1, scup CYP1C2, common carp CYP1C2 and zebra fish CYP1C2, respectively. Phylogenetic tree based on the amino acids sequences clearly shows tilapia CYP1C1 and scup CYP1C1 to be more closely related to each other than to CYP1C genes from other species. Furthermore, for measuring BaP induction of CYP1C1 mRNA in different organs of tilapia (O. niloticus), β-actin gene as internal control was selected based on previous studies to assess their expression variability. Real time RCR results revealed that there was a large increase in CYP1C1 mRNA in liver (43.1), intestine (5.1) and muscle (2.4). Copyright © 2011 Elsevier B.V. All rights reserved.

Risk Assessment for Children Exposed to Beach Sands Impacted by Oil Spill Chemicals.

PubMed

Black, Jennifer C; Welday, Jennifer N; Buckley, Brian; Ferguson, Alesia; Gurian, Patrick L; Mena, Kristina D; Yang, Ill; McCandlish, Elizabeth; Solo-Gabriele, Helena M

2016-08-27

Due to changes in the drilling industry, oil spills are impacting large expanses of coastlines, thereby increasing the potential for people to come in contact with oil spill chemicals. The objective of this manuscript was to evaluate the health risk to children who potentially contact beach sands impacted by oil spill chemicals from the Deepwater Horizon disaster. To identify chemicals of concern, the U.S. Environmental Protection Agency's (EPA's) monitoring data collected during and immediately after the spill were evaluated. This dataset was supplemented with measurements from beach sands and tar balls collected five years after the spill. Of interest is that metals in the sediments were observed at similar levels between the two sampling periods; some differences were observed for metals levels in tar balls. Although PAHs were not observed five years later, there is evidence of weathered-oil oxidative by-products. Comparing chemical concentration data to baseline soil risk levels, three metals (As, Ba, and V) and four PAHs (benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, and dibenz[a,h]anthracene) were found to exceed guideline levels prompting a risk assessment. For acute or sub-chronic exposures, hazard quotients, computed by estimating average expected contact behavior, showed no adverse potential health effects. For cancer, computations using 95% upper confidence limits for contaminant concentrations showed extremely low increased risk in the 10(-6) range for oral and dermal exposure from arsenic in sediments and from dermal exposure from benzo[a]pyrene and benz[a]anthracene in weathered oil. Overall, results suggest that health risks are extremely low, given the limitations of available data. Limitations of this study are associated with the lack of toxicological data for dispersants and oil-spill degradation products. We also recommend studies to collect quantitative information about children's beach play habits, which are necessary to more accurately assess exposure scenarios and health risks.

Circadian Regulation of Benzo[a]Pyrene Metabolism and DNA Adduct Formation in Breast Cells and the Mouse Mammary Gland.

PubMed

Schmitt, Emily E; Barhoumi, Rola; Metz, Richard P; Porter, Weston W

2017-03-01

The circadian clock plays a role in many biologic processes, yet very little is known about its role in metabolism of drugs and carcinogens. The purpose of this study was to define the impact of circadian rhythms on benzo-a-pyrene (BaP) metabolism in the mouse mammary gland and develop a circadian in vitro model for investigating changes in BaP metabolism resulting from cross-talk between the molecular clock and aryl hydrocarbon receptor. Female 129sv mice (12 weeks old) received a single gavage dose of 50 mg/kg BaP at either noon or midnight, and mammary tissues were isolated 4 or 24 hours later. BaP-induced Cyp1a1 and Cyp1b1 mRNA levels were higher 4 hours after dosing at noon than at 4 hours after dosing at midnight, and this corresponded with parallel changes in Per gene expression. In our in vitro model, we dosed MCF10A mammary cells at different times after serum shock to study how time of day shifts drug metabolism in cells. Analysis of CYP1A1 and CYP1B1 gene expression showed the maximum enzyme-induced metabolism response 12 and 20 hours after shock, as determined by ethoxyresorufin-O-deethylase activity, metabolism of BaP, and formation of DNA-BaP adducts. The pattern of PER-, BMAL-, and aryl hydrocarbon receptor-induced P450 gene expression and BaP metabolism was similar to BaP-induced Cyp1A1 and Cyp1B1 and molecular clock gene expression in mouse mammary glands. These studies indicate time-of-day exposure influences BaP metabolism in mouse mammary glands and describe an in vitro model that can be used to investigate the circadian influence on the metabolism of carcinogens. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Inflammation-associated extracellular β-glucuronidase alters cellular responses to the chemical carcinogen benzo[a]pyrene.

PubMed

Shi, Q; Haenen, G R; Maas, L; Arlt, V M; Spina, D; Vasquez, Y Riffo; Moonen, E; Veith, C; Van Schooten, F J; Godschalk, R W L

2016-09-01

Neutrophils infiltrate tissues during inflammation, and when activated, they release β-glucuronidase. Since inflammation is associated with carcinogenesis, we investigated how extracellular β-glucuronidase changed the in vitro cellular response to the chemical carcinogen benzo(a)pyrene (B[a]P). For this we exposed human liver (HepG2) and lung (A549) cells to B[a]P in the presence or absence of β-glucuronidase. β-Glucuronidase reduced B[a]P-induced expression of CYP1A1 and CYP1B1 at 6 h after exposure, which did not depend on β-glucuronidase activity, because the inhibitor D-saccharic acid 1,4-lactone monohydrate did not antagonize the effect of β-glucuronidase. On the other hand, the inhibitory effect of β-glucuronidase on CYP expression was dependent on signalling via the insulin-like growth factor receptor (IGF2R, a known receptor for β-glucuronidase), because co-incubation with the IGF2R inhibitor mannose-6-phosphate completely abolished the effect of β-glucuronidase. Extracellular β-glucuronidase also reduced the formation of several B[a]P metabolites and B[a]P-DNA adducts. Interestingly, at 24 h of exposure, β-glucuronidase significantly enhanced CYP expression, probably because β-glucuronidase de-glucuronidated B[a]P metabolites, which continued to trigger the aryl hydrocarbon receptor (Ah receptor) and induced expression of CYP1A1 (in both cell lines) and CYP1B1 (in A549 only). Consequently, significantly higher concentrations of B[a]P metabolites and DNA adducts were found in β-glucuronidase-treated cells at 24 h. DNA adduct levels peaked at 48 h in cells that were exposed to B[a]P and treated with β-glucuronidase. Overall, these data show that β-glucuronidase alters the cellular response to B[a]P and ultimately enhances B[a]P-induced DNA adduct levels.

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se; Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se; Bottai, Matteo, E-mail: Matteo.Bottai@ki.se

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNAmore » damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.« less

Appraisement, source apportionment and health risk of polycyclic aromatic hydrocarbons (PAHs) in vehicle-wash wastewater, Pakistan.

PubMed

Qamar, Zahir; Khan, Sardar; Khan, Anwarzeb; Aamir, Muhammad; Nawab, Javed; Waqas, Muhammad

2017-12-15

Vehicle-wash wastewater (VWW) contains elevated concentrations of different petrochemicals including polycyclic aromatic hydrocarbons (PAHs), a carcinogenic group of organic compounds. This study investigates the discharge of PAHs present in the untreated wastewater of vehicle-wash stations (VWS) located in district Peshawar, Pakistan. The data obtained was being novel with the detection of 16 USEPA PAHs (both individuals and total) and compared with earlier studies and international standards. The ∑16PAHs in wastewater from light vehicle-wash stations (LVWS) and heavy vehicle-wash stations (HVWS) ranged from 245-429μg/l and 957-1582μg/l, respectively. A significant difference (p<0.01) was observed in PAHs discharged from LVWS and HVWS. The projected ∑16PAHs discharge from both HVWS (92% of total generated PAHs) and LVWS (8%) was about 5109.9 g per annum. According to PAH diagnostic ratios, PAHs were both petrogenic (chrysene/benz(a)anthracene, low molecular weight/high molecular weight) and pyrogenic (phenanthrene/anthracene, fluoranthene/pyrene, fluoranthene/fluoranthene+pyrene) in origin. The highest toxic equivalent quotient (TEQ) value was shown by benzo(a)pyrene (21.6μg/l) followed by dibenz(ah)anthracene (9.81μg/l) in wastewater from HVWS. However, in LVWS the case was reversed with highest value (7.54μg/l) for dibenz(ah)anthracene followed by benzo(a)pyrene (3.54μg/l). The lowest TEQ value was indicated for phenanthrene (0.007μg/l) in wastewater of LVWS, while pyrene showed the lowest value (0.007μg/l) in wastewater of HVWS. The results indicated that VWS contribute significant amount of PAHs each year, which is of great concern regarding water quality, ecological and human health risk. This is the first systematic and comprehensive research related with generation of PAHs load per day, week, month and annum from VWS, their source apportionment and health effects in Pakistan. Copyright © 2017 Elsevier B.V. All rights reserved.

Toxicogenomic outcomes predictive of forestomach carcinogenesis following exposure to benzo(a)pyrene: Relevance to human cancer risk

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labib, Sarah, E-mail: Sarah.Labib@hc-sc.gc.ca; Guo, Charles H., E-mail: Charles.Guo@hc-sc.gc.ca; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca

2013-12-01

Forestomach tumors are observed in mice exposed to environmental carcinogens. However, the relevance of this data to humans is controversial because humans lack a forestomach. We hypothesize that an understanding of early molecular changes after exposure to a carcinogen in the forestomach will provide mode-of-action information to evaluate the applicability of forestomach cancers to human cancer risk assessment. In the present study we exposed mice to benzo(a)pyrene (BaP), an environmental carcinogen commonly associated with tumors of the rodent forestomach. Toxicogenomic tools were used to profile gene expression response in the forestomach. Adult Muta™Mouse males were orally exposed to 25, 50,more » and 75 mg BaP/kg-body-weight/day for 28 consecutive days. The forestomach was collected three days post-exposure. DNA microarrays, real-time RT-qPCR arrays, and protein analyses were employed to characterize responses in the forestomach. Microarray results showed altered expression of 414 genes across all treatment groups (± 1.5 fold; false discovery rate adjusted P ≤ 0.05). Significant downregulation of genes associated with phase II xenobiotic metabolism and increased expression of genes implicated in antigen processing and presentation, immune response, chemotaxis, and keratinocyte differentiation were observed in treated groups in a dose-dependent manner. A systematic comparison of the differentially expressed genes in the forestomach from the present study to differentially expressed genes identified in human diseases including human gastrointestinal tract cancers using the NextBio Human Disease Atlas showed significant commonalities between the two models. Our results provide molecular evidence supporting the use of the mouse forestomach model to evaluate chemically-induced gastrointestinal carcinogenesis in humans. - Highlights: • Benzo(a)pyrene-mediated transcriptomic response in the forestomach was examined. • The immunoproteosome subunits and MHC class I pathway were the most affected. • Keratinocyte differentiation associated gene expression changes were dose-dependent. • Molecular similarities exist between cancers of the forestomach and human stomach.« less

Altered expression of histone deacetylases, inflammatory cytokines and contractile-associated factors in uterine myometrium of Long Evans rats gestationally exposed to benzo[a]pyrene

PubMed Central

Laknaur, Archana; Foster, Terri-Lee; Bobb, Lesley E.; Ramesh, Aramandla; Ladson, Gwinnett M.; Hood, Darryl B.; Al-Hendy, Ayman; Thota, Chandrasekhar

2017-01-01

Etiology of preterm birth (PTB) is multifactorial; therefore, decreasing the incidence of PTB is a major challenge in the field of obstetrics. Epidemiological studies have reported an association between toxicants and PTB. However, there are no studies on the role of benzo[a]pyrene (BaP), an environmental toxicant, in the incidence of PTB. We first assessed the effects of BaP (150 and 300 μg kg−1 body weight) dosed via gavage from day 14 to 17 of pregnancy on gestation length in Long Evans rats. We further assessed the histopathology of the uterus, expression of inflammatory cytokines, contractile-associated factors, histone deacetylases (HDACs) and NFқB-p65 in myometrium collected on day 22 postpartum versus vehicle-treated controls. In our study, rats exposed to BaP delivered prematurely (P < 0.05) compared to control. Hematoxylin and eosin staining of uterus showed squamous metaplasia, glandular and stromal hyperplasia in BaP-exposed rats versus control. The concentrations of BaP metabolites measured by high-pressure liquid chromatography were higher in uterine myometrium of BaP-exposed rats while they were undetectable in controls. Quantitative real-time polymerase chain reaction showed significant increases in mRNA expression of interleukin-1β and -8, tumor necrosis factor-α, connexin 43, cyclo-oxygenase-2 and prostaglandin F2α receptor as compared to controls (P < 0.05). Western blot analysis revealed that BaP exposure caused decreases in class I HDACs 1 and 3 and increases in class II HDAC 5, cyclo-oxygenase-2 and nuclear translocation of NFκB-p65 relative to controls. Our results suggest that gestational exposure to BaP increases incidence of PTB through epigenetic changes that causes increases in the expression of contractile-associated factors through the NFκB pathway. PMID:26358852

Real-world automotive particulate matter and PAH emission factors and profile concentrations: Results from an urban tunnel experiment in Naples, Italy

NASA Astrophysics Data System (ADS)

Riccio, A.; Chianese, E.; Monaco, D.; Costagliola, M. A.; Perretta, G.; Prati, M. V.; Agrillo, G.; Esposito, A.; Gasbarra, D.; Shindler, L.; Brusasca, G.; Nanni, A.; Pozzi, C.; Magliulo, V.

2016-09-01

On-road particulate matter (PM) mass was measured during a sampling campaign in March of 2015 in the '4 giornate' tunnel in Naples, Italy. Two sets of samples were collected at both sides of the tunnel, each set representing the daily cycle at a 1 h time resolution. Distance-based - mass per kilometer - and fuel-based - mass per burned fuel - emission factors (EFs) were calculated using mass concentrations, traffic flow rates and wind speed as a function of fleet composition. Also, chemical analyses were performed for polycyclic aromatic hydrocarbons (PAHs). Due to the high traffic volume, particle mass concentration at the tunnel exit was always significantly elevated relative to entrance concentration; depending on the hour of the day, PM10 concentration ranged between 300 μg/m3, during the early afternoon, and 600 μg/m3 during rush hours at the tunnel exit. Correspondingly, PAHs achieved concentrations as high as 1450 ng/m3, and benzo(a)pyrene, a surely carcinogenic compound, achieved concentrations as high as 69 ng/m3, raising serious concerns in relation to population exposure close to this urban tunnel. Distance-based and fuel-based emission factors for CO2, PM10 and PAHs were estimated, but while the EF for CO2 was within the range of expected values, the present study found much higher EFs for particulate matter and PAHs. According to the national official statistics from ISPRA (the Italian Institute for the Protection and Research on Environment), derived from the COPERT database, we expected an EF for particulate matter of about 55 mg/km, but the EF estimated from measurements taken at both sides of the tunnel was about four times higher than that expected; also, benzo(a)pyrene achieved an average EF of 2.7 μg/km, about three times higher than that expected from the ISPRA database.

PAH concentrations simulated with the AURAMS-PAH chemical transport model over Canada and the USA

NASA Astrophysics Data System (ADS)

Galarneau, E.; Makar, P. A.; Zheng, Q.; Narayan, J.; Zhang, J.; Moran, M. D.; Bari, M. A.; Pathela, S.; Chen, A.; Chlumsky, R.

2014-04-01

The offline Eulerian AURAMS (A Unified Regional Air quality Modelling System) chemical transport model was adapted to simulate airborne concentrations of seven PAHs (polycyclic aromatic hydrocarbons): phenanthrene, anthracene, fluoranthene, pyrene, benz[a]anthracene, chrysene + triphenylene, and benzo[a]pyrene. The model was then run for the year 2002 with hourly output on a grid covering southern Canada and the continental USA with 42 km horizontal grid spacing. Model predictions were compared to ~5000 24 h-average PAH measurements from 45 sites, most of which were located in urban or industrial areas. Eight of the measurement sites also provided data on particle/gas partitioning which had been modelled using two alternative schemes. This is the first known regional modelling study for PAHs over a North American domain and the first modelling study at any scale to compare alternative particle/gas partitioning schemes against paired field measurements. The goal of the study was to provide output concentration maps of use to assessing human inhalation exposure to PAHs in ambient air. Annual average modelled total (gas + particle) concentrations were statistically indistinguishable from measured values for fluoranthene, pyrene and benz[a]anthracene whereas the model underestimated concentrations of phenanthrene, anthracene and chrysene + triphenylene. Significance for benzo[a]pyrene performance was close to the statistical threshold and depended on the particle/gas partitioning scheme employed. On a day-to-day basis, the model simulated total PAH concentrations to the correct order of magnitude the majority of the time. The model showed seasonal differences in prediction quality for volatile species which suggests that a missing emission source such as air-surface exchange should be included in future versions. Model performance differed substantially between measurement locations and the limited available evidence suggests that the model's spatial resolution was too coarse to capture the distribution of concentrations in densely populated areas. A more detailed analysis of the factors influencing modelled particle/gas partitioning is warranted based on the findings in this study.

2-Aminoanthracene, 5-fluorouracil, colchicine, benzo[a]pyrene, cadmium chloride and cytosine arabinoside tested in the in vitro mammalian cell micronucleus test (MNvit) in Chinese hamster ovary (CHO) cells at Covance Laboratories, Harrogate UK in support of OECD draft Test Guideline 487.

PubMed

Whitwell, James; Fowler, Paul; Allars, Sarah; Jenner, Karen; Lloyd, Melvyn; Wood, Debbie; Smith, Katie; Young, Jamie; Jeffrey, Laura; Kirkland, David

2010-10-29

The reference genotoxic agents 2-aminoanthracene (a metabolism dependent weak clastogen), 5-fluorouracil (a nucleoside analogue, characterised by a steep dose response profile), colchicine (an aneugen that inhibits tubulin polymerisation), benzo[a]pyrene (a polycyclic aromatic hydrocarbon requiring metabolic activation), cadmium chloride (an inorganic carcinogen), and cytosine arabinoside (a nucleoside analogue that inhibits the gap-filling step of excision repair) were tested in the in vitro micronucleus assay using the Chinese hamster ovary (CHO) cell line at Covance Laboratories, Harrogate, UK. All chemicals were treated in the absence and presence of cytokinesis block (via addition of cytochalasin B) with this work forming part of a collaborative evaluation of the toxicity measures recommended in the draft OECD Test Guideline 487 on the In vitro Mammalian Cell Micronucleus Test (MNvit). The toxicity measures used, detecting a possible combination of both cytostasis and cell death (though not cell death directly), were relative population doubling, relative increase in cell counts and relative cell counts for treatments in the absence of cytokinesis block, and replication index in the presence of cytokinesis block. All of the chemicals tested either gave marked positive increases in the percentage of micronucleated cells with and without cytokinesis block, or did not induce micronuclei at concentrations giving approximately 50-60% toxicity (cytostasis and cell death) or less by all of the toxicity measures used. The outcome from this series of tests supports the use of relative increase in cell counts and relative population doubling, as well as relative cell counts, as appropriate measures of cytotoxicity for the non-cytokinesis blocked in vitro micronucleus assay. Copyright © 2010 Elsevier B.V. All rights reserved.

Evaluation of a multi-endpoint assay in rats, combining the bone-marrow micronucleus test, the Comet assay and the flow-cytometric peripheral blood micronucleus test.

PubMed

Bowen, Damian E; Whitwell, James H; Lillford, Lucinda; Henderson, Debbie; Kidd, Darren; Mc Garry, Sarah; Pearce, Gareth; Beevers, Carol; Kirkland, David J

2011-05-18

With the publication of revised draft ICH guidelines (Draft ICH S2), there is scope and potential to establish a combined multi-end point in vivo assay to alleviate the need for multiple in vivo assays, thereby reducing time, cost and use of animals. Presented here are the results of an evaluation trial in which the bone-marrow and peripheral blood (via MicroFlow(®) flow cytometry) micronucleus tests (looking at potential chromosome breakage and whole chromosome loss) in developing erythrocytes or young reticulocytes were combined with the Comet assay (measuring DNA strand-breakage), in stomach, liver and blood lymphocytes. This allowed a variety of potential target tissues (site of contact, site of metabolism and peripheral distribution) to be assessed for DNA damage. This combination approach was performed with minimal changes to the standard and regulatory recommended sampling times for the stand-alone assays. A series of eight in vivo genotoxins (2-acetylaminofluorene, benzo[a]pyrene, carbendazim, cyclophosphamide, dimethylnitrosamine, ethyl methanesulfonate, ethyl nitrosourea and mitomycin C), which are known to act via different modes of action (direct- and indirect-acting clastogens, alkylating agents, gene mutagens, cross-linking and aneugenic compounds) were tested. Male rats were dosed at 0, 24 and 45 h, and bone marrow and peripheral blood (micronucleus endpoint), liver, whole blood and stomach (Comet endpoint) were sampled at three hours after the last dose. Comet and micronucleus responses were as expected based on available data for conventional (acute) stand-alone assays. All compounds were detected as genotoxic in at least one of the endpoints. The importance of evaluating both endpoints was highlighted by the uniquely positive responses for certain chemicals (benzo[a]pyrene and 2-acetylaminofluorene) with the Comet endpoint and certain other chemicals (carbendazim and mitomycin C) with the micronucleus endpoint. The data generated from these investigations demonstrate the suitability of the multi-endpoint design. 2011 Elsevier B.V. All rights reserved.

Curcumin and Vitamin E Protect against Adverse Effects of Benzo[a]pyrene in Lung Epithelial Cells

PubMed Central

Cai, Qingsong; Lv, Tangfeng; Singh, Kamaleshwar; Gao, Weimin

2014-01-01

Benzo[a]pyrene (BaP), a well-known environmental carcinogen, promotes oxidative stress and DNA damage. Curcumin and vitamin E (VE) have potent antioxidative activity that protects cells from oxidative stress and cellular damage. The objectives of the present study were to investigate the adverse effects of BaP on normal human lung epithelial cells (BEAS-2B), the potential protective effects of curcumin and VE against BaP-induced cellular damage, and the molecular mechanisms of action. MTT assay, flow cytometry, fluorescence microplate assay, HPLC, qRT-PCR, and western blot were performed to analyze cytotoxicity, cell cycle, reactive oxygen species (ROS), BaP diol-epoxidation (BPDE)-DNA adducts, gene expression, and protein expression, respectively. Curcumin or VE prevented cells from BaP-induced cell cycle arrest and growth inhibition, significantly suppressed BaP-induced ROS levels, and decreased BPDE-DNA adducts. While CYP1A1 and 1B1 were induced by BaP, these inductions were not significantly reduced by curcumin or VE. Moreover, the level of activated p53 and PARP-1 were significantly induced by BaP, whereas this induction was markedly reduced after curcumin and VE co-treatment. Survivin was significantly down-regulated by BaP, and curcumin significantly restored survivin expression in BaP-exposed cells. The ratio of Bax/Bcl-2 was also significantly increased in cells exposed to BaP and this increase was reversed by VE co-treatment. Taken together, BaP-induced cytotoxicity occurs through DNA damage, cell cycle arrest, ROS production, modulation of metabolizing enzymes, and the expression/activation of p53, PARP-1, survivin, and Bax/Bcl-2. Curcumin and VE could reverse some of these BaP-mediated alterations and therefore be effective natural compounds against the adverse effects of BaP in lung cells. PMID:24664296

Exposure of children to air pollution in the industrial zone of Metropolitan Area of Mexico City

NASA Astrophysics Data System (ADS)

Mugica-Alvarez, Violeta; Quintanilla-Vega, Betsabé; De Vizcaya-Ruiz, Andrea; Alvarado-Cruz, Isabel

2016-04-01

An air quality monitoring in three schools located in the most important industrial zone at the Northeast of the Metropolitan Area of Mexico City (MAMC) was conducted in order to determine the exposure of children to toxics contained in PM10. Particles were analyzed for metals, polycyclic aromatic hydrocarbons (PAH), organic and elemental carbon by ICP-AES, GC-MS and TOT (Sunset lab) respectively. Average concentration of PM10 was 108.4±11.6 μg/m3. Most abundant metals were Fe, Zn and Pb with concentrations ranged by 1.1-5.4 μg/m3, 0.3-2 μg/m3, and 0.18-0.63 μg/m3 respectively; the sum of the seventeen PAHs varied from 1.4 to 3.3 ng/m3 where most abundant PAH were indene[1,2,3-c,d]pyrene, benzo[b]fluoranthene, benzo[a]anthracene, chrysene, and benzo[a]pyrene. The sum of the seven carcinogenic PAH contributed in average with the 48% of the total mixture. Carcinogenic potential of PAH were obtained using toxic equivalent factors determined by Nisbet and La Goy which varied from 0.3 to 0.6 ng/ m3 of benzo[a]pyrene equivalent (BAPeq), this value is lower than the standard proposed for the European Community of 1 ng/ m3, but higher than the standard from the United Kingdom of 0.25 ng/ m3. Principal component analysis for source apportionment showed that vehicular and industrial emissions are the main sources of PM in the zone. In general, the concentrations of particles as well as concentration of metals and PAHs are lower than concentrations measured six year before, showing that the established measures have improved the air quality. Nevertheless these PM10 concentrations exceeded frequently the Mexican Standard and children are especially susceptible due to the higher risk to develop diseases if the exposure occurs at early age.

Benzo[a]pyrene bioavailability from pristine soil and contaminated sediment assessed using two in vitro models.

PubMed

Vasiluk, Luba; Pinto, Linda J; Walji, Zahra A; Tsang, Wing Shan; Gobas, Frank A P C; Eickhoff, Curtis; Moore, Margo M

2007-03-01

A major route of exposure to hydrophobic organic contaminants (HOCs), such as benzo[a]pyrene (BaP), is ingestion. Matrix-bound HOCs may become bioavailable after mobilization by the gastrointestinal fluids followed by sorption to the intestinal epithelium. The purpose of this research was to measure the bioavailability of [14C]-BaP bound to pristine soils or field-contaminated sediment using an in vitro model of gastrointestinal digestion followed by sorption to human enterocytes (Caco-2 cells) or to a surrogate membrane, ethylene vinyl acetate (EVA) thin film. Although Caco-2 cells had a twofold higher lipid-normalized fugacity capacity than EVA, [14C]-BaP uptake by Caco-2 lipids and EVA thin film demonstrated a linear relationship within the range of BaP concentrations tested. These results suggest that EVA thin film is a good membrane surrogate for passive uptake of BaP. The in vitro system provided enough sensitivity to detect matrix effects on bioavailability; after 5 h, significantly lower concentrations of [14C]-BaP were sorbed into Caco-2 cells from soil containing a higher percentage of organic matter compared to soil with a lower percentage of organic matter. The [14C]-BaP desorption rate from Caco-2 lipids consistently was twofold higher than from EVA thin film for all matrices tested. The more rapid kinetics observed with Caco-2 cells probably were due to the greater surface area available for absorption/desorption in the cells. After 5 h, the uptake of BaP into Caco-2 lipid was similar in live and metabolically inert Caco-2 cells, suggesting that the primary route of BaP uptake is by passive diffusion. Moreover, the driving force for uptake is the fugacity gradient that exists between the gastrointestinal fluid and the membrane.

Emissions into the Air from Bitumen and Rubber Bitumen-Implications for Asphalt Workers' Exposure.

PubMed

Nilsson, Patrik T; Bergendorf, Ulf; Tinnerberg, Håkan; Nordin, Erik; Gustavsson, Mats; Strandberg, Bo; Albin, Maria; Gudmundsson, Anders

2018-06-21

The risk among asphalt workers of developing adverse health effects may increase due to their occupational exposure. One area of special concern arises when rubber granules are mixed into bitumen to enhance asphalt properties. This research characterizes and compares bitumen and rubber bitumen regarding the emissions of and workers' exposure to particulates, polycyclic aromatic hydrocarbons (PAHs) and benzothiazole. A laboratory and a field study were carried out. In the laboratory, two types of bitumen, one with and one without rubber, were heated up to two temperatures (140°C and 160°C). The concentrations and chemical compositions of the emissions were determined. In the field at asphalt work sites, both emissions and worker exposure measurements were performed. The methods applied included direct-reading sampling techniques next to the asphalt work area and personal sampling techniques on asphalt workers. The exposure measurements on asphalt workers for respirable dust, total dust, particle number and mass, and total PAH concentrations showed similar concentrations when both standard and rubber bitumen were used. The asphalt-surfacing machine operators were the workers with the highest observed exposure followed by the screed operators and roller drivers. Both laboratory and field measurements showed higher concentrations of benzothiazole when rubber bitumen was used, up to 7.5 times higher in the laboratory. The levels of naphthalene, benzo(a)pyrene, and total particles were lower for both types compared with the Swedish occupational exposure limits, 8-h time weighted average concentrations. Benzo(a)pyrene exceeded however the health-based guideline value given by the WHO for both types of bitumen. The study concludes that several air pollutants such as benzothiazole and PAHs are emitted into the air during asphalt work, but it is not evident if exposure to rubber bitumen possesses a higher risk than exposure to standard bitumen in terms of asphalt worker exposure.

A common carcinogen benzo[a]pyrene causes neuronal death in mouse via microglial activation.

PubMed

Dutta, Kallol; Ghosh, Debapriya; Nazmi, Arshed; Kumawat, Kanhaiya Lal; Basu, Anirban

2010-04-01

Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert.

Antioxidant responses to benzo[a]pyrene, tributyltin and their mixture in the spleen of Sebasticus marmoratus.

PubMed

Wu, Yu-Qiong; Wang, Chong-Gang; Wang, Yun; Zhao, Yang; Chen, Yi-Xin; Zuo, Zheng-Hong

2007-01-01

It has been reported that there is an interaction between Benzo[a]pyrene (BaP), a widespread carcinogenic polycyclic aromatic hydrocarbon, and tributyltin (TBT), an organometal used as an antifouling biocide. This study was therefore designed to examine the potential in vivo influence of BaP, TBT and their mixture on splenic antioxidant defense systems of Sebastiscus marmoratus. The fish were exposed to water containing environmentally relevant concentrations of BaP, TBT and their mixture. Spleens were collected for biochemical analysis after exposure for 7, 25, 50 d and after recovery for 7, 20 d. Cotreatment with BaP and TBT for 7 d potentiated the induction of glutathione peroxidase (GPx) activity by BaP or TBT alone. The cotreatment for 25 and 50 d resulted in inhibition of GPx activity, which was similar to the effect of TBT. Splenic glutathione S-transferase (GST) activities were significantly elevated in S. marmoratus exposed to BaP starting from 7 d and remained high up to 25 d. However, no further activity change was found with prolonged exposure. Cotreatment of BaP and TBT primarily inhibited the GST activity, which was similar to the effect of TBT. Cotreatment with BaP and TBT for 25 or 50 d potentiated the depletion of GSH (glutathione) by BaP or TBT alone. MDA (malondialdehyde) contents in spleen of S. marmoratus were not significantly altered compared with the control during the test period. Spleen, as an immune organ, is sensitive to exposure of BaP or TBT. It should have an effective mechanism to counteract oxidative damage. Antioxidative defense systems in spleen of S. marmoratus should be considered as potential biomarkers. Short-term exposure of BaP or TBT could result in induction of antioxidant defense system. A significant decrease of these indices, such as GSH, GST, GPx might indicate more severe contamination.

Risk Assessment for Children Exposed to Beach Sands Impacted by Oil Spill Chemicals

PubMed Central

Black, Jennifer C.; Welday, Jennifer N.; Buckley, Brian; Ferguson, Alesia; Gurian, Patrick L.; Mena, Kristina D.; Yang, Ill; McCandlish, Elizabeth; Solo-Gabriele, Helena M.

2016-01-01

Due to changes in the drilling industry, oil spills are impacting large expanses of coastlines, thereby increasing the potential for people to come in contact with oil spill chemicals. The objective of this manuscript was to evaluate the health risk to children who potentially contact beach sands impacted by oil spill chemicals from the Deepwater Horizon disaster. To identify chemicals of concern, the U.S. Environmental Protection Agency’s (EPA’s) monitoring data collected during and immediately after the spill were evaluated. This dataset was supplemented with measurements from beach sands and tar balls collected five years after the spill. Of interest is that metals in the sediments were observed at similar levels between the two sampling periods; some differences were observed for metals levels in tar balls. Although PAHs were not observed five years later, there is evidence of weathered-oil oxidative by-products. Comparing chemical concentration data to baseline soil risk levels, three metals (As, Ba, and V) and four PAHs (benzo[a]pyrene, benz[a]anthracene, benzo[b]fluoranthene, and dibenz[a,h]anthracene) were found to exceed guideline levels prompting a risk assessment. For acute or sub-chronic exposures, hazard quotients, computed by estimating average expected contact behavior, showed no adverse potential health effects. For cancer, computations using 95% upper confidence limits for contaminant concentrations showed extremely low increased risk in the 10−6 range for oral and dermal exposure from arsenic in sediments and from dermal exposure from benzo[a]pyrene and benz[a]anthracene in weathered oil. Overall, results suggest that health risks are extremely low, given the limitations of available data. Limitations of this study are associated with the lack of toxicological data for dispersants and oil-spill degradation products. We also recommend studies to collect quantitative information about children’s beach play habits, which are necessary to more accurately assess exposure scenarios and health risks. PMID:27618904

Co-exposure of the organic nanomaterial fullerene C₆₀ with benzo[a]pyrene in Danio rerio (zebrafish) hepatocytes: evidence of toxicological interactions.

PubMed

Ferreira, Josencler L Ribas; Lonné, María Noelia; França, Thiago A; Maximilla, Naiana R; Lugokenski, Thiago H; Costa, Patrícia G; Fillmann, Gilberto; Antunes Soares, Félix A; de la Torre, Fernando R; Monserrat, José María

2014-02-01

Compounds from the nanotechnology industry, such as carbon-based nanomaterials, are strong candidates to contaminate aquatic environments because their production and disposal have exponentially grown in a few years. Previous evidence shows that fullerene C60, a carbon nanomaterial, can facilitate the intake of metals or PAHs both in vivo and in vitro, potentially amplifying the deleterious effects of these toxicants in organisms. The present work aimed to investigate the effects of fullerene C60 in a Danio rerio (zebrafish) hepatocyte cell lineage exposed to benzo[a]pyrene (BaP) in terms of cell viability, oxidative stress parameters and BaP intracellular accumulation. Additionally, a computational docking was performed to investigate the interaction of the fullerene C60 molecule with the detoxificatory and antioxidant enzyme πGST. Fullerene C60 provoked a significant (p<0.05) loss in cellular viability when co-exposed with BaP at 0.01, 0.1 and 1.0 μg/L, and induced an increase (p<0.05) in BaP accumulation in the cells after 3 and 4h of exposure. The levels of reactive oxygen species (ROS) in the cells exposed to BaP were diminished (p<0.05) by the fullerene addition, and the increase of the GST activity observed in the BaP-only treated cells was reduced to the basal levels by co-exposure to fullerene. However, despite the potential of the fullerene molecule to inhibit π GST activity, demonstrated by the computational docking, the nanomaterial did not significantly (p>0.05) alter the enzyme activity when added to GST purified extracts from the zebrafish hepatocyte cells. These results show that fullerene C60 can increase the intake of BaP into the cells, decreasing cell viability and impairing the detoxificatory response by phase II enzymes, such as GST, and this latter effect should be occurring at the transcriptional level. Copyright © 2013 Elsevier B.V. All rights reserved.

Multigenerational effects of benzo[a]pyrene exposure on survival and developmental deformities in zebrafish larvae

PubMed Central

Corrales, Jone; Thornton, Cammi; White, Mallory; Willett, Kristine L.

2014-01-01

In the aquatic environment, adverse outcomes from dietary polycyclic aromatic hydrocarbon (PAH) exposure are poorly understood, and multigenerational developmental effects following exposure to PAHs are in need of exploration. Benzo[a]pyrene (BaP), a model PAH, is a recognized carcinogen and endocrine disruptor. Here adult zebrafish (F0) were fed 0, 10, 114, or 1012 μg BaP/g diet at a feed rate of 1% body weight twice/day for 21 days. Eggs were collected and embryos (F1) were raised to assess mortality and time to hatch at 24, 32, 48, 56, 72, 80, and 96 hours post fertilization (hpf) before scoring developmental deformities at 96 hpf. F1 generation fish were raised to produce the F2 generation followed by the F3 and F4 generations. Mortality significantly increased in the higher dose groups of BaP (2.3 and 20 μg BaP/g fish) in the F1 generation while there were no differences in the F2, F3, or F4 generations. In addition, premature hatching was observed among the surviving fish in the higher dose of the F1 generation, but no differences were found in the F2 and F3 generations. While only the adult F0 generation was BaP-treated, this exposure resulted in multigenerational phenotypic impacts on at least two generations (F1 and F2). Body morphology deformities (shape of body, tail, and pectoral fins) were the most severe abnormality observed, and these were most extreme in the F1 generation but still present in the F2 but not F3 generations. Craniofacial structures (length of brain regions, size of optic and otic vesicles, and jaw deformities), although not significantly affected in the F1 generation, emerged as significant deformities in the F2 generation. Future work will attempt to molecularly anchor the persistent multigenerational phenotypic deformities noted in this study caused by BaP exposure. PMID:24440964

Hydrodynamic modelling of the influence of stormwater and combined sewer overflows on receiving water quality: Benzo(a)pyrene and copper risks to recreational water.

PubMed

Björklund, Karin; Bondelind, Mia; Karlsson, Anna; Karlsson, Dick; Sokolova, Ekaterina

2018-02-01

The risk from chemical substances in surface waters is often increased during wet weather, due to surface runoff, combined sewer overflows (CSOs) and erosion of contaminated land. There are strong incentives to improve the quality of surface waters affected by human activities, not only from ecotoxicity and ecosystem health perspectives, but also for drinking water and recreational purposes. The aim of this study is to investigate the influence of urban stormwater discharges and CSOs on receiving water in the context of chemical health risks and recreational water quality. Transport of copper (Cu) and benzo[a]pyrene (BaP) in the Göta River (Sweden) was simulated using a hydrodynamic model. Within the 16 km modelled section, 35 CSO and 16 urban stormwater point discharges, as well as the effluent from a major wastewater treatment plant, were included. Pollutant concentrations in the river were simulated for two rain events and investigated at 13 suggested bathing sites. The simulations indicate that water quality guideline values for Cu are exceeded at several sites, and that stormwater discharges generally give rise to higher Cu and BaP concentrations than CSOs. Due to the location of point discharges and the river current inhibiting lateral mixing, the north shore of the river is better suited for bathing. Peak concentrations have a short duration; increased concentrations of the pollutants may however be present for several days after a rain event. Monitoring of river water quality indicates that simulated Cu and BaP concentrations are in the same order of magnitude as measured concentrations. It is concluded that hydrodynamic modelling is a useful tool for identifying suitable bathing sites in urban surface waters and areas of concern where mitigation measures should be implemented to improve water quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genetic polymorphisms in 19q13.3 genes associated with alteration of repair capacity to BPDE-DNA adducts in primary cultured lymphocytes.

PubMed

Xiao, Mingyang; Xiao, Sha; Straaten, Tahar van der; Xue, Ping; Zhang, Guopei; Zheng, Xiao; Zhang, Qianye; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Zhu, Guolian; Lu, Xiaobo

2016-12-01

Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells.

PubMed Central

Green, J L; Jones, B C; Reed, G A

1994-01-01

Sulfur dioxide (SO2) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials after a 4-hr incubation period. The net nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 1. Figure 2. Figure 3. Figure 3. Figure 3. Figure 3. Figure 3. Figure 3. Figure 4. PMID:8033853

Quantity and quality of stormwater collected from selected stormwater outfalls at industrial sites, Fort Gordon, Georgia, 2012

USGS Publications Warehouse

Nagle, Doug D.

2013-01-01

Samples from sites SWR11–3, SWR11–4, and SWR11–5 were analyzed for 83 volatile and semivolatile organic compounds. Eight polycyclic aromatic hydrocarbon compounds, benzo[a]pyrene, benzo[b]fluoranthene, benzo[ghi]perylene, benzo[k]fluoranthene, chrysene, indeno[1,2,3-cd]pyrene, phenanthrene, and pyrene, were detected at all three sites. Of the 86 volatile and semivolatile organic compounds that were analyzed in stormwater samples from heating and cooling sites, 15 (18 percent) were detected at site SWR11–3, 12 (14 percent) were detected at site SWR11–4, and 17 (20 percent) were detected at site SWR11–5.

Emission patterns of diesel-powered passenger cars. Part II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Braddock, J.N.; Gabele, P.A.

An experimental program was conducted to characterize the gaseous and particulate emissions from a 1975 Peugeot 504D light duty diesel-powered vehicle. The vehicle was tested over the 1975 Federal Test Procedure, Highway Fuel Economy Test, and Sulfate Emissions Test driving cycles using four different fuels covering a fair range of composition, density, and sulfur content. In addition to fuel economy and regulated gaseous emission measurements of hydrocarbons, carbon monoxide, and oxides of nitrogen, emission measurements were also obtained for non-regulated pollutants including sulfur dioxide, sulfates, aldehydes, benzo(a)pyrene, carbonyl sulfide, hydrogen cyanide, nonreactive hydrocarbons, and particulate matter. The results are discussedmore » in terms of emission trends due to either fuel type or driving cycle influence.« less

Continuous human cell lines and method of making same

DOEpatents

Stampfer, M.R.

1985-07-01

Substantially genetically stable continuous human cell lines derived from normal human mammary epithelial cells (HMEC) and processes for making and using the same. In a preferred embodiment, the cell lines are derived by treating normal human mammary epithelial tissue with a chemical carcinogen such as benzo(a)pyrene. The novel cell lines serve as useful substrates for elucidating the potential effects of a number of toxins, carcinogens and mutagens as well as of the addition of exogenous genetic material. The autogenic parent cells from which the cell lines are derived serve as convenient control samples for testing. The cell lines are not neoplastically transformed, although they have acquired several properties which distinguish them from their normal progenitors. 2 tabs.

Priority PAHs in orthodox black tea during manufacturing process.

PubMed

Grover, Inderpreet Singh; Singh, Satnam; Pal, Bonamali

2013-08-01

Orthodox black tea is obtained from fresh leaves followed by withering, rolling, fermentation and drying. The presence of 16 priority polycyclic aromatic hydrocarbons (PAHs) was studied in fresh leaves and at various stages of manufacturing. Benzo(a)pyrene (2A: probable human carcinogen) was found in dried tea leaves only whereas, naphthalene (2B: probable human carcinogen) was present during all the stages of manufacturing. Dry tea leaves showed higher content of total 16 PAHs (∑PAHs) about 3 and 211 times than present in withered and dried leaves, respectively. Chrysene, benzo[g,h,i]perylene, indendo[1,2,3-c,d]pyrene, dibenzo[a,h]pyrene and benzo[a]antracene were not found during manufacturing stages of tea.

Bacterial Degradation of Aromatic Compounds

PubMed Central

Seo, Jong-Su; Keum, Young-Soo; Li, Qing X.

2009-01-01

Aromatic compounds are among the most prevalent and persistent pollutants in the environment. Petroleum-contaminated soil and sediment commonly contain a mixture of polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatics. Aromatics derived from industrial activities often have functional groups such as alkyls, halogens and nitro groups. Biodegradation is a major mechanism of removal of organic pollutants from a contaminated site. This review focuses on bacterial degradation pathways of selected aromatic compounds. Catabolic pathways of naphthalene, fluorene, phenanthrene, fluoranthene, pyrene, and benzo[a]pyrene are described in detail. Bacterial catabolism of the heterocycles dibenzofuran, carbazole, dibenzothiophene, and dibenzodioxin is discussed. Bacterial catabolism of alkylated PAHs is summarized, followed by a brief discussion of proteomics and metabolomics as powerful tools for elucidation of biodegradation mechanisms. PMID:19440284

Sediments from stormwater drainage system as sorbents of organic and inorganic pollutants

NASA Astrophysics Data System (ADS)

Sałata, Aleksandra; Dąbek, Lidia

2017-11-01

The study presents the results of tests aimed at determining variations in concentrations of polycyclic aromatic hydrocarbons (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo[a]anthracene, chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[a, h]anthracene, benzo[g, h, i]perylene and indeno[1, 2, 3-c, d]pyrene) and heavy metals (copper, cadmium, chromium, nickel, lead and zinc) in the sediments from the stormwater sewer system. Results of this study were then compared to Polish regulations and established ecological screening values to determine their potential risk to environment. The results suggest that stormwater sediments are moderately contaminated with PAHs and heavy metals according to domestic regulations and highly contaminated according to ecological benchmarks.

[Preliminary determination of organic pollutants in agricultural fertilizers].

PubMed

Mo, Ce-hui; Li, Yun-hui; Cai, Quan-ying; Zeng, Qiao-yun; Wang, Bo-guang; Li, Hai-qin

2005-05-01

Organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) in agricultural fertilizers are new problem deserved more study. Eight kinds of organic pollutants including 43 compounds classified as US EPA priority pollutants in twenty one agricultural fertilizers which were universally used in China were determined by Gas chromatography-mass spectrum (GC-MS). Three kinds of organic pollutants including more than 5 compounds were detected in most fertilizers, composing mainly of phthalic acid esters (PAEs), nitrobenzenes (NBs) and polycyclic aromatic hydrocarbons (PAHs). There were 26 compounds detected in at least one fertilizer, five of them especially PAEs detected in most fertilizer and even in all fertilizers. Benzo(a)pyrene, a strongly carcinogenic compound was detected in two fertilizers. Higher concentrations of compounds were determined in those fertilizers such as multifunction compound fertilizers and coated fertilizers.

Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines.

PubMed

Padma, P R; Amonkar, A J; Bhide, S V

1989-03-01

Epidemiological studies have implicated chewing tobacco alone to be more hazardous than chewing tobacco with betel quid. Experimental studies have shown that betel leaf is antimutagenic against standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since the tobacco-specific N-nitrosamines (TSNA) are the only carcinogens present in unburnt forms of tobacco, including chewing tobacco, we tested the effect of an extract of betel leaf against the mutagenicity of the two important TSNA, viz., N'-nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, using the Ames Salmonella/microsome assay with TA100 +S9 and the in vivo micronucleus test. In both the test systems it was observed that betel leaf extract suppressed the mutagenic effects of both the nitrosamines to a significant extent.

Biosensors and other medical and environmental probes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobson, K.B.

1996-12-31

The author presents a overview of work at Oak Ridge National Laboratory directed toward the development of biosensors which can be used to monitor for an array of medical and environmental effects. The article describes the variety of problems which have been addressed by development of such sensors, and the range of staff who have been actively involved in this effort. The first such sensor developed at ORNL was an optical fiber whose end was treated with an antibody which would react with the carcinogen benzo(a)pyrene (BaP). Section titles from the article provide an idea of the breadth of applicationsmore » addressed: medical telesensors; microcantilevers; detecting cancer and health abnormalities; bioreporters; miniaturized devices; biosensors and DNA analysis; lipids in bacteria and human fingerprints; and anthropometry.« less

Heterogeneous ozonation reactions of PAHs and fatty acid methyl esters in biodiesel particulate matter

NASA Astrophysics Data System (ADS)

Kasumba, John; Holmén, Britt A.

2018-02-01

Numerous studies have examined the oxidation of PAHs found in diesel particulate matter (PM) by ozone, but no studies have investigated the ozone oxidation of biodiesel exhaust PM. Fatty acid methyl esters (FAMEs), found in high abundance in biodiesel PM, can potentially alter the kinetics of the reactions between atmospheric oxidants such as ozone and particle-phase PAHs. In this study, the heterogeneous reactivity of 16 EPA PAHs upon 24 h exposure to 0.4 ppm ozone in the presence (PAH + FAMES) and absence (PAH-only) of FAMEs was investigated at room temperature and 50% relative humidity. The ozone-reactivity of the PAHs detected in 20% biodiesel (B20) exhaust PM was also investigated. In the absence of FAMEs, the pseudo-first order ozone reaction rate constant, kO 3 , of PAHs varied from 0.086 ± 0.030 hr-1 (chrysene) to 0.184 ± 0.078 hr-1 (anthracene). In the presence of FAMEs, kO 3 of the PAHs varied between 0.013 ± 0.012 hr-1 (benzo[b]fluoranthene) and 0.168 ± 0.028 hr-1 (benzo[a]pyrene), and with the exception of benzo[a]pyrene, the kO 3 of PAHs were 1.2-8 times lower compared to those obtained during the PAH-only ozone exposure. Only one PAH, benzo[a]pyrene (BaP), did not show a significant change in kO3 with addition of FAMEs. Phenanthrene, fluoranthene, and pyrene, the only PAHs detected in the B20 PM, had kO 3 values about 4 times lower in B20 PM than those obtained when spiked PAHs-only were exposed to ozone. The kO 3 values of phenanthrene and fluoranthene in the B20 PM were 2 times higher than rates obtained when the PAH mix was exposed to ozone in the presence of the FAMEs. In contrast, pyrene's kO 3 in the B20 PM was about 2 times lower than that obtained for the PAH + FAMEs exposure. Observed differences in PAH behavior demonstrate individual PAH heterogeneous reactivity with gas-phase ozone is sensitive to PAH (vapor pressure, solubility/sorption to matrix components, chemical reactivity) as well as substrate properties (PAH and O3 diffusivity in the matrix that may evolve with reaction progress). Saturated FAMEs were not reactive with ozone (kO 3 range = 0.004 ± 0.003 to 0.012 ± 0.026 hr-1), but compared to PAHs, up to two times higher kO 3 was measured for the unsaturated FAMEs (range 0.087 ± 0.015 to 0.329 ± 0.023 hr-1) during PAH + FAMEs exposures. These changes in substrate composition during atmospheric aging would be expected to affect PAH diffusivity and therefore heterogeneous reactivity over time. The factor of 1.2-8 decreased heterogeneous reactivity of PAHs in the presence of the FAMEs mix and the B20 PM matrix suggests that the presence of FAMEs in the diesel fuel supply may lead to increased PAH atmospheric lifetimes and longer range PAH transport. Predictive methods to quantify changes in PAH reactivity with gas-phase oxidants as a function of substrate composition and characteristics (viscosity, polarity, degree of unsaturation) are needed as biodiesel is increasingly present in our diesel engine fuel supply from a variety of feedstocks at different blend ratios.

Benzo[a]pyrene (BP) DNA adduct formation in DNA repair–deficient p53 haploinsufficient [Xpa(−/−)p53(+/−)] and wild-type mice fed BP and BP plus chlorophyllin for 28 days

PubMed Central

Poirier, Miriam C.

2012-01-01

We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a]pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(−/−)p53(+/−) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N 2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)–DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(−/−)p53(+/−) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(−/−)p53(+/−) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(−/−)p53(+/−) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP–DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(−/−)p53(+/−) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH–DNA adduct levels consistently in human organs. PMID:22828138

Analysis of 200 food items for benzo[a]pyrene and estimation of its intake in an epidemiologic study.

PubMed

Kazerouni, N; Sinha, R; Hsu, C H; Greenberg, A; Rothman, N

2001-05-01

Animal studies have shown that dietary intake of benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), causes increased levels of tumors at several sites, particularly in the upper gastrointestinal tract. However, the role of dietary intake of BaP and cancer in humans is not clear. We created a BaP database of selected food products that could be linked to Food Frequency Questionnaires (FFQs) to estimate BaP intake. BaP levels were measured for each food line-item (composite samples) which consisted of a variety of foods in a FFQ. Composite sample parts were derived from the Second National Health and Nutrition Examination Survey (NHANES II) which represents the most common food items consumed by the general population. Meat samples were cooked by different techniques in controlled conditions, and by various restaurants and fast-food chains. Non-meat products were purchased from the major national supermarket chains. The quantities of BaP were measured using a thin-layer chromatography (TLC)/spectrofluorometer technique and were highly correlated with both BaP (r=0.99) [corrected] and sum of carcinogenic PAH (r=0.98) measured by HPLC technique. We linked our database to the results from a FFQ and estimated the daily BaP intake of various food items in 228 subjects in the Washington, DC metropolitan area. The highest levels of BaP (up to about 4 ng BaP/g of cooked meat) were found in grilled/barbecued very well done steaks and hamburgers and in grilled/barbecued well done chicken with skin. BaP concentrations were lower in meats that were grilled/barbecued to medium done and in all broiled or pan-fried meat samples regardless of doneness level. The BaP levels in non-meat items were generally low. However, certain cereals and greens (e.g. kale, collard greens) had levels up to 0.5 ng/g. In our population, the bread/cereal/grain, and grilled/barbecued meat, respectively, contributed 29 and 21 percent to the mean daily intake of BaP. This database may be helpful in initial attempts to assess dietary BaP exposures in studies of cancer etiology.

DNA single strand breakage, DNA adducts, and sister chromatid exchange in lymphocytes and phenanthrene and pyrene metabolites in urine of coke oven workers.

PubMed Central

Popp, W; Vahrenholz, C; Schell, C; Grimmer, G; Dettbarn, G; Kraus, R; Brauksiepe, A; Schmeling, B; Gutzeit, T; von Bülow, J; Norpoth, K

1997-01-01

OBJECTIVES: To investigate the specificity of biological monitoring variables (excretion of phenanthrene and pyrene metabolites in urine) and the usefulness of some biomarkers of effect (alkaline filter elution, 32P postlabelling assay, measurement of sister chromatid exchange) in workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: 29 coke oven workers and a standardised control group were investigated for frequencies of DNA single strand breakage, DNA protein cross links (alkaline filter elution assay), sister chromatid exchange, and DNA adducts (32P postlabelling assay) in lymphocytes. Phenanthrene and pyrene metabolites were measured in 24 hour urine samples. 19 different PAHs (including benzo(a)pyrene, pyrene, and phenanthrene) were measured at the workplace by personal air monitoring. The GSTT1 activity in erythrocytes and lymphocyte subpopulations in blood was also measured. RESULTS: Concentrations of phenanthrene, pyrene, and benzo(a)pyrene in air correlated well with the concentration of total PAHs in air; they could be used for comparisons of different workplaces if the emission compositions were known. The measurement of phenanthrene metabolites in urine proved to be a better biological monitoring variable than the measurement of 1-hydroxypyrene. Significantly more DNA strand breaks in lymphocytes of coke oven workers were found (alkaline filter elution assay); the DNA adduct rate was not significantly increased in workers, but correlated with exposure to PAHs in a semiquantitative manner. The number of sister chromatid exchanges was lower in coke oven workers but this was not significant; thus counting sister chromatid exchanges was not a good variable for biomonitoring of coke oven workers. Also, indications for immunotoxic influences (changes in lymphocyte subpopulations) were found. CONCLUSIONS: The measurement of phenanthrene metabolites in urine seems to be a better biological monitoring variable for exposure to PAHs than measurement of hydroxypyrene. The alkaline filter elution assay proved to be the most sensitive biomarker for genotoxic damage, whereas the postlabelling assay was the only one with some specificity for DNA alterations caused by known compounds. PMID:9155778

Effects of subchronic benzo(a)pyrene exposure on neurotransmitter receptor gene expression in the rat hippocampus related with spatial learning and memory change.

PubMed

Qiu, Chongying; Cheng, Shuqun; Xia, Yinyin; Peng, Bin; Tang, Qian; Tu, Baijie

2011-11-18

Exposure of laboratory rats to Benzo(a)pyrene (BaP), an environmental contaminant with its high lipophilicify which is widely dispersed in the environment and can easily cross the blood brain barrier presenting in the central nervous system, is associated with impaired learning and memory. The purpose of the research was to examine whether subchronic exposure to BaP affects spatial learning and memory, and how it alters normal gene expression in hippocampus, as well as selection of candidate genes involving neurotransmitter receptor attributed to learning and memory. Morris water maze (MWM) was used to evaluate behavioral differences between BaP-treated and vehicle-treated groups. To gain a better insight into the mechanism of BaP-induced neurotoxicity on learning and memory, we used whole genome oligo microarrays as well as Polymerase Chain Reaction (PCR) to assess the global impact of gene expression. Male Sprague-Dawley rats were intraperitoneally injected with 6.25mg/kg of BaP or vehicle for 14 weeks. The results from the Morris water maze (MWM) test showed that rats treated with BaP exhibited significantly higher mean latencies as compared to vehicle controls. BaP exposure significantly decreased the number of crossing the platform and the time spent in the target area. After the hippocampus was collected from each rat, total RNA was isolated. Microarray and PCR revealed that exposure to BaP affected mRNA expression of neurotransmitter receptors. The web tool DAVID was used to analyze the significantly enriched gene ontology (GO) and KEGG pathways in the differentially expressed genes. Analysis showed that the most significantly affected gene ontology category was behavior. Furthermore, the fourth highest significantly affected gene ontology category was learning and memory. KEGG molecular pathway analysis showed that "neuroactive ligand-receptor interaction" was affected by BaP with highest statistical significance, and 9 candidate neurotransmitter receptor genes involving learning and memory were selected out. Our results revealed a close link between behavioral changes and altered neurotransmitter receptor gene expression in BaP-treated rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Association between mutation spectra and stable and unstable DNA adduct profiles in Salmonella for benzo[a]pyrene and dibenzo[a,l]pyrene.

PubMed

DeMarini, David M; Hanley, Nancy M; Warren, Sarah H; Adams, Linda D; King, Leon C

2011-09-01

Benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) are two polycyclic aromatic hydrocarbons (PAHs) that exhibit distinctly different mutagenicity and carcinogenicity profiles. Although some studies show that these PAHs produce unstable DNA adducts, conflicting data and arguments have been presented regarding the relative roles of these unstable adducts versus stable adducts, as well as oxidative damage, in the mutagenesis and tumor-mutation spectra of these PAHs. However, no study has determined the mutation spectra along with the stable and unstable DNA adducts in the same system with both PAHs. Thus, we determined the mutagenic potencies and mutation spectra of BP and DBP in strains TA98, TA100 and TA104 of Salmonella, and we also measured the levels of abasic sites (aldehydic-site assay) and characterized the stable DNA adducts ((32)P-postlabeling/HPLC) induced by these PAHs in TA104. Our results for the mutation spectra and site specificity of stable adducts were consistent with those from other systems, showing that DBP was more mutagenic than BP in TA98 and TA100. The mutation spectra of DBP and BP were significantly different in TA98 and TA104, with 24% of the mutations induced by BP in TA98 being complex frameshifts, whereas DBP produced hardly any of these mutations. In TA104, BP produced primarily GC to TA transversions, whereas DBP produced primarily AT to TA transversions. The majority (96%) of stable adducts induced by BP were at guanine, whereas the majority (80%) induced by DBP were at adenine. Although BP induced abasic sites, DBP did not. Most importantly, the proportion of mutations induced by DBP at adenine and guanine paralleled the proportion of stable DNA adducts induced by DBP at adenine and guanine; however, this was not the case for BP. Our results leave open a possible role for unstable DNA adducts in the mutational specificity of BP but not for DBP. Published by Elsevier B.V.

Inhibition of aryl hydrocarbon receptor transactivation and DNA adduct formation by CYP1 isoform-selective metabolic deactivation of benzo[a]pyrene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Endo, Kaori; Uno, Shigeyuki; Seki, Taiichiro

Benzo[a]pyrene (BaP), a polyaromatic hydrocarbon produced by the combustion of cigarettes and coke ovens, is a known procarcinogen. BaP activates the aryl hydrocarbon receptor (AhR) and induces the expression of a battery of genes, including CYP1A1, which metabolize BaP to toxic compounds. The possible role of CYP1 enzymes in mediating BaP detoxification or metabolic activation remains to be elucidated. In this study, we assessed the effects of CYP1 enzymes (CYP1A1, CYP1A2 and CYP1B1) on BaP-induced AhR transactivation and DNA adduct formation in HEK293 cells and HepG2 cells. Transfection of CYP1A1 and CYP1B1, but not CYP1A2, suppressed BaP-induced activation of AhR.more » Expression of CYP1A1 and CYP1A2, but not CYP1B1, inhibited DNA adduct formation in BaP-treated HepG2 cells. These results indicate that CYP1A1 and CYP1B1 play a role in deactivation of BaP on AhR and that CYP1A1 and CYP1A2 are involved in BaP detoxification by suppressing DNA adduct formation. BaP treatment did not induce DNA adduct formation in HEK293 cells, even after transfection of CYP1 enzymes, suggesting that expression of CYP1 enzymes is not sufficient for DNA adduct formation. Lower expression of epoxide hydrolase and higher expression of glutathione S-transferase P1 (GSTP1) and GSTM1/M2 were observed in HEK293 cells compared with HepG2 cells. Dynamic expression of CYP1A1, CYP1A2 and CYP1B1 along with expression of other enzymes such as epoxide hydrolase and phase II enzymes may determine the detoxification or metabolic activation of BaP.« less

Transcriptome analysis reveals novel insights into the response of low-dose benzo(a)pyrene exposure in male tilapia.

PubMed

Colli-Dula, Reyna Cristina; Fang, Xiefan; Moraga-Amador, David; Albornoz-Abud, Nacira; Zamora-Bustillos, Roberto; Conesa, Ana; Zapata-Perez, Omar; Moreno, Diego; Hernandez-Nuñez, Emanuel

2018-06-08

Despite a wide number of toxicological studies that describe benzo[a]pyrene (BaP) effects, the metabolic mechanisms that underlie these effects in fish are largely unknown. Of great concern is the presence of BaP in aquatic systems, especially those in close proximity to human activity leading to consumption of potentially contaminated foods. BaP is a known carcinogen and it has been reported to have adverse effects on the survival, development and reproduction of fish. The purpose of this study was to investigate if a low dose of BaP can alter genes and key metabolic pathways in the liver and testis in male adult tilapia, and whether these could be associated with biological endpoints disruption. We used both high-throughput RNA-Sequencing to assess whole genome gene expression following repeated intraperitoneal injections of 3 mg/kg of BaP (every 6 days for 26 days) and morphometric endpoints as indicators of general health. Condition factor (K) along with hepatosomatic and gonadosomatic indices (morphometric parameters) were significantly lower in BaP-treated fish than in controls. BaP exposure induced important changes in the gene expression pattern in liver and testis as revealed by both Pathway and Gene Ontology (GO) analyses. Alterations that were shared by both tissues included arachidonic acid metabolism, androgen receptor to prostate-specific antigen signaling, and insulin-associated effects on lipogenesis. The most salient liver-specific effects included: biological processes involved in detoxification, IL6-associated insulin resistance, mTOR hyperactivation, mitotic cytokinesis, spindle pole and microtubule binding. BaP effects that were confined to the testis included: immune system functions, inflammatory response, estrogen and androgen metabolic pathways. Taken together, gene expression and morphometric end point data indicate that the reproductive success of adult male tilapia could be compromised as a result of BaP exposure. These results constitute new insights on the mechanism of action of low dose BaP in a non-model organism (tilapia). Copyright © 2018 Elsevier B.V. All rights reserved.

Involvement of Alpha-PAK-Interacting Exchange Factor in the PAK1–c-Jun NH2-Terminal Kinase 1 Activation and Apoptosis Induced by Benzo[a]pyrene

PubMed Central

Yoshii, Shigeto; Tanaka, Masamitsu; Otsuki, Yoshiro; Fujiyama, Toshiharu; Kataoka, Hideki; Arai, Hajime; Hanai, Hiroyuki; Sugimura, Haruhiko

2001-01-01

Benzo[a]pyrene [B(a)P], a potent procarcinogen found in combustion products such as diesel exhaust and cigarette smoke, has been recently shown to activate the c-Jun NH2-terminal kinase 1 (JNK1) and induce caspase-3-mediated apoptosis in Hepa1c1c7 cells. However, the molecules of the signaling pathway that control the mitogen-activated protein kinase cascades induced by B(a)P and the interaction between those and apoptosis by B(a)P have not been well defined. We report here that B(a)P promoted Cdc42/Rac1, p21-activated kinase 1 (PAK1), and JNK1 activities in 293T and HeLa cells. Moreover, alpha-PAK-interacting exchange factor (α PIX) mRNA and its protein expression were upregulated by B(a)P. While overexpression of an active mutant of α PIX (ΔCH) facilitated B(a)P-induced activation of Cdc42/Rac1, PAK1, and JNK1, overexpression of mutated αPIX (L383R, L384S), which lacks guanine nucleotide exchange factor activity, SH3 domain-deleted αPIX (Δ SH3), which lacks the ability to bind PAK, kinase-negative PAK1 (K299R), and kinase-negative SEK1 (K220A, K224L) inhibited B(a)P-triggered JNK1 activation. Interestingly, overexpression of αPIX (Δ CH) and a catalytically active mutant PAK1 (T423E) accelerated B(a)P-induced apoptosis in HeLa cells, whereas αPIX (Δ SH3), PAK1 (K299R), and SEK 1 (K220A, K224L) inhibited B(a)P-initiated apoptosis. Finally, a preferential caspase inhibitor, Z-Asp-CH2-DCB, strongly blocked the αPIX (Δ CH)-enhanced apoptosis in cells treated with B(a)P but did not block PAK1/JNK1 activation. Taken together, these results indicate that αPIX plays a crucial role in B(a)P-induced apoptosis through activation of the JNK1 pathway kinases. PMID:11564864

Comparison of oral bioavailability of benzo[a]pyrene in soils using rat and swine and the implications for human health risk assessment.

PubMed

Duan, Luchun; Naidu, Ravi; Liu, Yanju; Dong, Zhaomin; Mallavarapu, Megharaj; Herde, Paul; Kuchel, Tim; Semple, Kirk T

2016-09-01

There are many uncertainties concerning variations in benzo[a]pyrene (B[a]P) soil guidelines protecting human health based on carcinogenic data obtained in animal studies. Although swine is recognised as being much more representative of the human child in terms of body size, gut physiology and genetic profile the rat/mice model is commonly used in practice. We compare B[a]P bioavailability using a rat model to that estimated in a swine model, to investigate the correlation between these two animal models. This may help reduce uncertainty in applying bioavailability to human health risk assessment. Twelve spiked soil samples and a spiked silica sand (reference material) were dosed to rats in parallel with a swine study. B[a]P bioavailability was estimated by the area under the plasma B[a]P concentration-time curve (AUC) and faecal excretion as well in the rats. Direct comparison between the two animal models was made for: firstly, relative bioavailability (RB) using AUC assay; and secondly, the two assays in the rat model. Both AUC and faecal excretion assays showed linear dose-response for the reference material. However, absolute bioavailability was significantly higher when using faecal excretion assay (p<0.001). In aged soils faecal excretion estimated based on solvent extraction was not accurate due to the form of non-extractable fraction through ageing. A significant correlation existed between the two models using RB for soil samples (RBrat=0.26RBswine+17.3, R(2)=0.70, p<0.001), despite the regression slope coefficient revealing that the rat model would underestimate RB by about one quarter compared to using swine. In the comparison employed in this study, an interspecies difference of four in RB using AUC assay was identified between the rat and swine models regarding pharmacokinetic differences, which supported the body weight scaling method recommended by US EPA. Future research should focus on the carcinogenic competency (pharmacodynamics) used in experiment animals and humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

The rapid alveolar absorption of diesel soot-adsorbed benzo[a]pyrene: bioavailability, metabolism and dosimetry of an inhaled particle-borne carcinogen.

PubMed

Gerde, P; Muggenburg, B A; Lundborg, M; Dahl, A R

2001-05-01

Exposure to diesel exhaust may contribute to lung cancer in humans. It remains unclear whether the carbonaceous core of the soot particle or its coat of adsorbed/condensed organics contributes most to cancer risk. Equally unclear are the extent and rate at which organic procarcinogens desorb from soot particles in the lungs following inhalation exposure and the extent of their metabolic activation in the lungs. To explore the basic relationship between a model polycyclic aromatic hydrocarbon (PAH) and a typical carrier particle, we investigated the rate and extent of release and metabolic fate of benzo[a]pyrene (BaP) adsorbed on the carbonaceous core of diesel soot. The native organic content of the soot had been denuded by toluene extraction. Exogenous BaP was adsorbed onto the denuded soot as a surface coating corresponding to 25% of a monomolecular layer. Dogs were exposed by inhalation to an aerosol bolus of the soot-adsorbed BAP: Following deposition in the alveolar region a fraction of BaP was rapidly desorbed from the soot and quickly absorbed into the circulation. Release rates then decreased drastically. When coatings reached approximately 16% of a monolayer the remaining BaP was not bioavailable and was retained on the particles after 5.6 months in the lung. However, the bioavailability of particles transported to the lymph nodes was markedly higher; after 5.6 months the surface coating of BaP was reduced to 10%. BaP that remained adsorbed on the soot surface after this period was approximately 30% parent compound. In contrast, the rapidly released pulse of BaP, which was quickly absorbed through the alveolar epithelium after inhalation, appeared mostly unmetabolized in the circulation, along with low concentrations of phase I and phase II BaP metabolites. However, within approximately 1 h this rapidly absorbed fraction of BaP was systemically metabolized into mostly conjugated phase II metabolites. The results indicate that absorption through the alveolar epithelium is an important route of entry to the circulation of unmetabolized PAHS:

Spectral characterization of the fluorescent components present in humic substances, fulvic acid and humic acid mixed with pure benzo(a)pyrene solution.

PubMed

El Fallah, Rawa; Rouillon, Régis; Vouvé, Florence

2018-06-15

The fate of benzo(a)pyrene (BaP), a ubiquitous contaminant reported to be persistent in the environment, is largely controlled by its interactions with the soil organic matter. In the present study, the spectral characteristics of fluorophores present in the physical fractions of the soil organic matter were investigated in the presence of pure BaP solution. After extraction of humic substances (HSs), and their fractionation into fluvic acid (FA) and humic acid (HA), two fluorescent compounds (C 1 and C 2 ) were identified and characterized in each physical soil fraction, by means of fluorescence excitation-emission matrices (FEEMs) and Parallel Factor Analysis (PARAFAC). Then, to each type of fraction having similar DOC content, was added an increasing volume of pure BaP solution in attempt to assess the behavior of BaP with the fluorophores present in each one. The application of FEEMs-PARAFAC method validated a three-component model that consisted of the two resulted fluorophores from HSs, FA and HA (C 1 and C 2 ) and a BaP-like fluorophore (C 3 ). Spectral modifications were noted for components C 2 HSs (C 2 in humic substances fraction) (λex/λem: 420/490-520 nm), C 2 FA (C 2 in fulvic acid fraction) (λex/λem: 400/487(517) nm) and C 1 HA (C 1 in humic acid fraction) (λex/λem: 350/452(520) nm). We explored the impact of increasing the volume of the added pure BaP solution on the scores of the fluorophores present in the soil fractions. It was found that the scores of C 2 HSs, C 2 FA, and C 1 HA increased when the volume of the added pure BaP solution increased. Superposition of the excitation spectra of these fluorophores with the emission spectrum of BaP showed significant overlaps that might explain the observed interactions between BaP and the fluorescent compounds present in SOM physical fractions. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitation of enantiomers of r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]-pyrene in human urine: evidence supporting metabolic activation of benzo[a]pyrene via the bay region diol epoxide.

PubMed

Hecht, Stephen S; Hochalter, Jon Bradley

2014-09-01

Benzo[a]pyrene (BaP), a potent polycyclic aromatic hydrocarbon carcinogen, is widely distributed in the human environment. All humans are exposed to BaP through the diet and contact with the general environment; cigarette smokers have higher exposure. An important pathway of BaP metabolism proceeds through formation of diol epoxides including the 'bay region diol epoxide' 7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [BaP-(7R,8S)-diol-(9S,10R)-epoxide] and the 'reverse diol epoxide' 9S,10R-dihydroxy-7R,8S-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene [BaP-(9S,10R)-diol-(7R,8S)-epoxide]. The bay region diol epoxide is considered a major ultimate carcinogen of BaP based on studies in cell culture and laboratory animals, but the available data in humans are less convincing. The bay region diol epoxide and the reverse diol epoxide react with H2O to produce enantiomeric BaP-tetraols that are excreted in the urine. We used chiral stationary-phase high-performance liquid chromatography and gas chromatography-negative ion chemical ionisation-tandem mass spectrometry to quantify these enantiomeric BaP-tetraols in the urine of 25 smokers and 25 non-smokers. The results demonstrated that the BaP-tetraol enantiomer representing the carcinogenic bay region diol epoxide pathway accounted for 68±6% (range 56-81%) of total BaP-tetraol in smokers and 64±6% (range 46-78%) in non-smokers. Levels of the major BaP-tetraol enantiomer decreased by 75% in smokers who quit smoking. These data provide convincing evidence in support of the bay region diol epoxide mechanism of BaP carcinogenesis in humans. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Opposing seasonal trends for polycyclic aromatic hydrocarbons and PM10: Health risk and sources in southwest Mexico City

NASA Astrophysics Data System (ADS)

Amador-Muñoz, Omar; Bazán-Torija, S.; Villa-Ferreira, S. A.; Villalobos-Pietrini, Rafael; Bravo-Cabrera, José Luis; Munive-Colín, Zenaida; Hernández-Mena, Leonel; Saldarriaga-Noreña, H.; Murillo-Tovar, M. A.

2013-03-01

This study reports the measurement of polycyclic aromatic hydrocarbons (PAHs) in airborne particles ≤ 10 μm (PM10) during four years. Seasonal variation was observed for PM10 and PAH in southwest Mexico City, with major mass concentrations during the dry season (November-April). A non linear decreasing trend of PM10 was observed during this period, while a linear increase (in the four years) was obtained for benzo[a]pyrene (88 pg m- 3), phenanthrene (29 pg m- 3), fluoranthene (88 pg m- 3), and benzo[ghi]perylene (438 pg m- 3). Coronene also showed an increasing trend but it was nonlinear. This suggests that air control strategies implemented by the government contributed to maintaining PM10 under the 24 h maximum limit and resulted in a decreasing trend during this period. However, these strategies did not result in controlling some organic constituents with mutagenic and/or carcinogenic properties as it is the case of benzo[a]pyrene. The annual average of this PAH exceeded the UK recommendation. It was estimated a median (10th-90th) lifetime health risk of 7.6 (3.4-17.2) additional cases of cancer per 10 million people in this zone exists and the health risk of PAH is almost three times greater in dry seasons than it is in rainy seasons. Specific humidity, temperature and wind speed acted as cleaners for PM10 and PAH from the atmosphere. PAH diagnostic ratios and correlation and principal component analyses suggest incomplete combustion from gasoline and diesel engines as the main contributor to PAH found in southwest Mexico City, where factor 1 grouped all PAH emitted from gasoline engines during first three years. During last year, factor 1 only grouped PAH markers of diesel engines. This suggests a change of emission amounts between gasoline and diesel combustion sources or a contribution of other source(s) which changed the PAH profiles. During four years retene was always separated from factors which grouped the rest of PAH, due to its wood combustion origin.

Complex metabolic interactions between benzo(a)pyrene and tributyltin in presence of dichlorodiphenyltrichloroethane in South American catfish Rhamdia quelen.

PubMed

Oliveira, Heloísa H P; Babin, Mathieu; Garcia, Juan Ramon Esquivel; Filipak Neto, Francisco; Randi, Marco A F; Oliveira Ribeiro, Ciro A; Pelletier, Émilien

2013-10-01

In an attempt to explore complex metabolic interactions between toxicants present in polluted freshwater, hepatic metabolism of benzo(a)pyrene (BaP) and tributyltin (TBT) in fish was investigated when these compounds were administrated alone, mixed together and along with dichlorodiphenyltrichloroethane (DDT). Ten Rhamdia quelen per group were treated with a single intra-peritoneal (IP) dose (5-day experiment) or three successive doses (15-day experiment) either containing BaP (0.3; 3 or 30mgkg(-1)) or TBT (0.03; 0.3 or 3mgkg(-1)) or a combination of BaP+TBT, BaP+DDT, TBT+DDT and BaP+TBT+DDT under their respective lower doses, with DDT dose kept at 0.03mgkg(-1). Tetrahydroxy-benzo(a)pyrene (BaP-tetrol-I), and dibutyltin (DBT) and monobutyltin (MBT) were analyzed to assess BaP and TBT hepatic metabolism, respectively. A significant difference in BaP-tetrol-I concentration was observed in liver and bile between the lowest and the highest doses of BaP in both 5 and 15-day experiments. In the 15-day experiment, the presence of TBT with BaP reduced the amount of BaP-tetrol-I in bile compared to the BaP alone. The time of exposure and the number of doses affected BaP-tetrol-I concentration in the bile of fish exposed to BaP 0.3mgkg(-1) and BaP+DDT. TBT and its metabolites concentrations showed a dose-dependent increase in the liver in both experiments and in the bile in the 5-day experiment. TBT at its lowest dose was completely metabolized into DBT and MBT in the liver in the 15-day experiment. No TBT metabolites were detected in the bile of fish exposed to the mixtures in the 5-day experiment, except for a small MBT amount found in BaP+TBT+DDT. This study strengthens the hypothesis of a metabolic interaction between BaP and TBT in fish and suggests DDT as an important third player when present in the mixture. Copyright © 2013 Elsevier Inc. All rights reserved.

Spectral characterization of the fluorescent components present in humic substances, fulvic acid and humic acid mixed with pure benzo(a)pyrene solution

NASA Astrophysics Data System (ADS)

El Fallah, Rawa; Rouillon, Régis; Vouvé, Florence

2018-06-01

The fate of benzo(a)pyrene (BaP), a ubiquitous contaminant reported to be persistent in the environment, is largely controlled by its interactions with the soil organic matter. In the present study, the spectral characteristics of fluorophores present in the physical fractions of the soil organic matter were investigated in the presence of pure BaP solution. After extraction of humic substances (HSs), and their fractionation into fluvic acid (FA) and humic acid (HA), two fluorescent compounds (C1 and C2) were identified and characterized in each physical soil fraction, by means of fluorescence excitation-emission matrices (FEEMs) and Parallel Factor Analysis (PARAFAC). Then, to each type of fraction having similar DOC content, was added an increasing volume of pure BaP solution in attempt to assess the behavior of BaP with the fluorophores present in each one. The application of FEEMs-PARAFAC method validated a three-component model that consisted of the two resulted fluorophores from HSs, FA and HA (C1 and C2) and a BaP-like fluorophore (C3). Spectral modifications were noted for components C2HSs (C2 in humic substances fraction) (λex/λem: 420/490-520 nm), C2FA (C2 in fulvic acid fraction) (λex/λem: 400/487(517) nm) and C1HA (C1 in humic acid fraction) (λex/λem: 350/452(520) nm). We explored the impact of increasing the volume of the added pure BaP solution on the scores of the fluorophores present in the soil fractions. It was found that the scores of C2HSs, C2FA, and C1HA increased when the volume of the added pure BaP solution increased. Superposition of the excitation spectra of these fluorophores with the emission spectrum of BaP showed significant overlaps that might explain the observed interactions between BaP and the fluorescent compounds present in SOM physical fractions.

Effects of polycyclic aromatic hydrocarbons on microbial community structure and PAH ring hydroxylating dioxygenase gene abundance in soil.

PubMed

Sawulski, Przemyslaw; Clipson, Nicholas; Doyle, Evelyn

2014-11-01

Development of successful bioremediation strategies for environments contaminated with recalcitrant pollutants requires in-depth knowledge of the microorganisms and microbial processes involved in degradation. The response of soil microbial communities to three polycyclic aromatic hydrocarbons, phenanthrene (3-ring), fluoranthene (4-ring) and benzo(a)pyrene (5-ring), was examined. Profiles of bacterial, archaeal and fungal communities were generated using molecular fingerprinting techniques (TRFLP, ARISA) and multivariate statistical tools were employed to interpret the effect of PAHs on community dynamics and composition. The extent and rate of PAH removal was directly related to the chemical structure, with the 5-ring PAH benzo(a)pyrene degraded more slowly than phenathrene or fluoranthene. Bacterial, archaeal and fungal communities were all significantly affected by PAH amendment, time and their interaction. Based on analysis of clone libraries, Actinobacteria appeared to dominate in fluoranthene amended soil, although they also represented a significant portion of the diversity in phenanthrene amended and unamended soils. In addition there appeared to be more γ-Proteobacteria and less Bacteroidetes in soil amended with either PAH compared to the control. The soil bacterial community clearly possessed the potential to degrade PAHs as evidenced by the abundance of PAH ring hydroxylating (PAH-RHDα) genes from both gram negative (GN) and gram positive (GP) bacteria in PAH-amended and control soils. Although the dioxygenase gene from GP bacteria was less abundant in soil than the gene associated with GN bacteria, significant (p < 0.001) increases in the abundance of the GP PAH-RHDα gene were observed during phenanthrene and fluoranthene degradation, whereas there was no significant difference in the abundance of the GN PAH-RHDα gene during the course of the experiment. Few studies to-date have examined the effect of pollutants on more than one microbial community in soil. The current study provides information on the response of soil bacterial, archaeal and fungal communities during the degradation of three priority pollutants and contributes to a knowledge base that can inform the development of effective bioremediation strategies for contaminated sites.

TERT regulates telomere-related senescence and apoptosis through DNA damage response in male germ cells exposed to BPDE in vitro and to B[a]P in vivo.

PubMed

Ling, Xi; Yang, Wang; Zou, Peng; Zhang, Guowei; Wang, Zhi; Zhang, Xi; Chen, Hongqiang; Peng, Kaige; Han, Fei; Liu, Jinyi; Cao, Jia; Ao, Lin

2018-04-01

Increasing evidence shows that impaired telomere function is associated with male infertility, and various environmental factors are believed to play a pivotal role in telomerase deficiency and telomere shortening. Benzo[a]pyrene (B[a]P), a ubiquitous pollutant of polycyclic aromatic hydrocarbons (PAHs), can act as a reproductive toxicant; however, the adverse effect of B[a]P on telomeres in male reproductive cells has never been studied, and the related mechanisms remain unclear. In this study, we explored the effects of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the active metabolite of B[a]P, on telomere dysfunction in mouse spermatocyte-derived cells (GC-2) and also the potential role of telomerase in BPDE-induced spermatogenic cell damage. The results showed that BPDE induced cell viability inhibition, senescence, and apoptosis in GC-2 cells in a dose-dependent manner. Shortened telomeres, telomere-associated DNA damage, reduced telomerase activity, and TERT expression were also observed in BPDE-treated cells, accompanied with the activation of DNA damage response pathway (ATM/Chk1/p53/p21). Moreover, by establishing the TERT knockdown and re-expression cell models, we found that TERT regulated telomere length and the expression of DNA damage response-related proteins to influence senescence and apoptosis in GC-2 cells. These in vitro findings were further confirmed in vivo in the testicular cells of rats orally administrated with B[a]P for 7 days. B[a]P treatment resulted in histological lesions, apoptosis, and senescence in the testes of rats, which were accompanied by shortened telomeres, reduced levels of TERT protein, and increased expression of DNA damage response-related proteins. In conclusion, it can be concluded that TERT-mediated telomere dysfunction contributes to B[a]P- and BPDE-induced senescence and apoptosis through DNA damage response in male reproductive cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Compartmental analysis of the disposition of benzo[a]pyrene in rats.

PubMed

Bevan, D R; Weyand, E H

1988-11-01

We have previously reported the disposition of benzo[a]pyrene (B[a]P) and its metabolites in male Sprague-Dawley rats following intratracheal instillation of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1986) Cancer Res., 46, 5655-5661]. In some experiments, cannulas were implanted in the bile duct of the animals prior to administration of [3H]B[a]P [Weyand, E.H. and Bevan, D.R. (1987) Drug Metab. Disposition, 15, 442-448]. Based on these data, we have developed a compartmental model of the distribution of radioactivity to provide a quantitative description of the fate of B[a]P and its metabolites in rats. Modeling of the distribution of radioactivity was performed using the Simulation, Analysis and Modeling (SAAM) and conversational SAAM (CONSAM) computer programs. Compartments in the model included organs into which the largest amounts of radioactivity were distributed as well as pathways for excretion of radioactivity from the animals. Data from animals with and without cannulas implanted in the bile duct were considered simultaneously during modeling. Radioactivity was so rapidly absorbed from the lungs that an absorption phase into blood was not apparent at the earliest sampling times. Using the model of extrapolate to shorter times, it was predicted that the maximum amount of radioactivity was present in blood within 2 min after administration. In addition, considerable recycling of radioactivity back to lungs from blood was predicted by the model. Transfer of radioactivity from blood to liver and carcass (skin, muscle, bones, fat and associated blood) also was extensive. Carcass was modeled as the sum of two compartments to obtain agreement between the model and experimental data. The model accounted for enterohepatic circulation of B[a]P metabolites; data also required that intestinal secretion be included in the model. Quantitative data obtained from compartmental analysis included rate constants for transfer of radioactivity among compartments as well as statistical parameters indicating the identifiability of the rate constants. That the model is consistent with two sets of data, those obtained in animals with and without a biliary cannula, indicates its potential utility in predicting the disposition of B[a]P and its metabolites in vivo.

Size distribution and sources of 37 toxic species of particulate polycyclic aromatic hydrocarbons during summer and winter in Baoshan suburban area of Shanghai, China.

PubMed

Wang, Qingyue; Kobayashi, Keisuke; Wang, Weiqian; Ruan, Jie; Nakajima, Daisuke; Yagishita, Mayuko; Lu, Senlin; Zhang, Wenchao; Suzuki, Miho; Saitou, Tomoya; Sekiguchi, Kazuhiko; Sankoda, Kenshi; Takao, Yuji; Nagae, Masaki; Terasaki, Masanori

2016-10-01

The objectives of this study were to assess the size-segregated distribution and sources of 37 different species of particulate polycyclic aromatic hydrocarbons (PAHs) in a suburban area of Shanghai metropolitan City, China. The ambient particulate sampling was carried out on the rooftop of a five-stories building in Baoshan campus of Shanghai University. An Andersen high-volume air sampler was employed to collect ambient size-segregated particulate matter during summer of August to September and winter of November to December 2015. The high toxic PAHs were determined by a gas chromatography mass spectrometry. The concentrations of total PAHs in suspended particulate matter (SPM) and PM1.1 (suspended particulate matter below 1.1μm in diameter) in the suburban area of Shanghai were 4.58-14.5ng/m(3) and 1.82-8.56ng/m(3), respectively in summer, and 43.6-160ng/m(3) and 23.2-121ng/m(3), separately in winter. 1,8-Naphthalic anhydride (1,8-NA) showed the highest concentration among 37 different species of PAHs in the suburban area of Shanghai. The concentrations of high molecular PAHs (e.g. 5-6 ring PAHs) followed a nearly unimodal size distribution with the highest peaks in PM1.1. The diagnostic ration qualitatively indicated that PAHs in SPM of Shanghai were mainly derived from motor-vehicle or petroleum combustion in summer and from coal and biomass combustion in winter. According to the calculated toxicity equivalency factors based on the methods of Nisbet and Lagoy and the potency equivalency factors (PEF) recommended by U.S. EPA, the highest contributors in the total carcinogenicity of the PAHs in SPM and PM1.1 were dibenzo[a,h]pyrene (46.2% and 45.0% in summer), benzo[a]pyrene (44.4% and 43.8% in winter) and benz[j]aceanthrylene (80.2% and 83.1% in summer and 83.1% and 84.0% in winter), respectively. Therefore, benzo[a]pyrene seemed to be a lower contributor than other carcinogenic PAHs. Copyright © 2016 Elsevier B.V. All rights reserved.

Organophosphorus pesticides enhance the genotoxicity of benzo(a)pyrene by modulating its metabolism.

PubMed

Hreljac, Irena; Filipic, Metka

2009-12-01

Organophosphorus compounds (OPs) are widely used as pesticides. They act primarily as neurotoxins, but there is increasing evidence for secondary mechanisms of their toxicity. We have shown that the model OPs, methyl parathion (PT) and methyl paraoxon (PO), are genotoxic. Benzo(a)pyrene (BaP) is a widespread environmental genotoxin found in cigarette smoke, polluted air and grilled food. As people are constantly exposed to low concentrations of BaP and also to OPs, the aim of this study was to determine possible synergistic effects of PT and PO on BaP-induced genotoxicity. In the bacterial reverse mutation assay, PT and PO increased the number of BaP-induced mutations. The comet assay with human hepatoma HepG2 cells showed that BaP-induced DNA strand breaks were increased by PT but slightly decreased by PO. Using the acellular comet assay with UVC-induced DNA strand breaks, we observed a decrease in DNA migration, indicating that OPs cause cross-linking, thus interfering with comet assay results. In HepG2 cells the two OPs induced micronuclei formation at very low doses (0.01 microg/ml) and together with BaP, a more than additive increase of micronuclei was observed, confirming their co-genotoxic effect. We demonstrated for the first time that PT and PO modulate the metabolic activation of BaP. Addition of PT or PO increased aldo-keto reductase (AKR1C1/2) levels in the presence of BaP, while cytochrome 1A (CYP1A) mRNA expression and activity were decreased. Further, specific inhibition of CYP1A had no effect on BaP or OP+BaP-induced micronuclei, whereas inhibition of AKR1C dramatically decreased the number of micronuclei induced by BaP or OP+BaP. Based on these results we propose that co-genotoxicity results from OPs mediated modulation of BaP metabolism, favouring the induction of AKR1C enzymes known to catalyse the formation of DNA reactive BaP o-quinones and the production of reactive oxygen species.

Dietary benzo(a)pyrene intake during pregnancy and birth weight: associations modified by vitamin C intakes in the Norwegian Mother and Child Cohort Study (MoBa).

PubMed

Duarte-Salles, Talita; Mendez, Michelle A; Meltzer, Helle Margrete; Alexander, Jan; Haugen, Margaretha

2013-10-01

Maternal exposure to polycyclic aromatic hydrocarbons (PAH) during pregnancy has been associated with reduced fetal growth. However, the role of diet, the main source of PAH exposure among non-smokers, remains uncertain. To assess associations between maternal exposure to dietary intake of the genotoxic PAH benzo(a)pyrene [B(a)P] during pregnancy and birth weight, exploring potential effect modification by dietary intakes of vitamins C, E and A, hypothesized to influence PAH metabolism. This study included 50,651 women in the Norwegian Mother and Child Cohort Study (MoBa). Dietary B(a)P and nutrient intakes were estimated based on total consumption obtained from a food frequency questionnaire (FFQ) and estimated based on food composition data. Data on infant birth weight were obtained from the Medical Birth Registry of Norway (MBRN). Multivariate regression was used to assess associations between dietary B(a)P and birth weight, evaluating potential interactions with candidate nutrients. The multivariate-adjusted coefficient (95%CI) for birth weight associated with maternal energy-adjusted B(a)P intake was -20.5g (-31.1, -10.0) in women in the third compared with the first tertile of B(a)P intake. Results were similar after excluding smokers. Significant interactions were found between elevated intakes of vitamin C (>85mg/day) and dietary B(a)P during pregnancy for birth weight (P<0.05), but no interactions were found with other vitamins. The multivariate-adjusted coefficients (95%CI) for birth weight in women in the third compared with the first tertile of B(a)P intake were -44.4g (-76.5, -12.3) in the group with low vitamin C intakes vs. -17.6g (-29.0, -6.1) in the high vitamin C intake group. The results suggest that higher prenatal exposure to dietary B(a)P may reduce birth weight. Lowering maternal intake of B(a)P and increasing dietary vitamin C intake during pregnancy may help to reduce any adverse effects of B(a)P on birth weight. © 2013.

Separation and characterization of gall bladder bile metabolites from speckled trout, Salvelinus fontinalis, exposed to individual polycyclic aromatic compounds.

PubMed

Leonard, J D; Hellou, J

2001-03-01

Speckled trout, Salvelinus fontinalis, were orally exposed to individual polycyclic aromatic compounds (PACs) represented by benzo[a]pyrene, carbazole, chrysene, dibenzofuran, dibenzothiophene, fluorene, phenanthrene, and pyrene. Fish were sacrificed 7 d after exposure and the gall bladder removed for bile analysis. High pressure liquid chromatography (HPLC) with fluorescence (F) and ultraviolet (UV) detection was used to determine the presence of PAC derivatives in the bile without pretreatment. Glucuronide conjugates were predominant in all exposures with variable amounts (0-53%) of phenols and starting material. Identification of compounds was confirmed by selective extraction of less polar nonconjugated PACs and enzymatic hydrolysis of water-soluble material. This was followed by HPLC and/or gas chromatography-mass spectrometry (GCMS) characterization of the produced phenols. Total metabolite levels varied widely among compounds.

Growth-altering microbial interactions are responsive to chemical context

PubMed Central

2017-01-01

Microbial interactions are ubiquitous in nature, and are equally as relevant to human wellbeing as the identities of the interacting microbes. However, microbial interactions are difficult to measure and characterize. Furthermore, there is growing evidence that they are not fixed, but dependent on environmental context. We present a novel workflow for inferring microbial interactions that integrates semi-automated image analysis with a colony stamping mechanism, with the overall effect of improving throughput and reproducibility of colony interaction assays. We apply our approach to infer interactions among bacterial species associated with the normal lung microbiome, and how those interactions are altered by the presence of benzo[a]pyrene, a carcinogenic compound found in cigarettes. We found that the presence of this single compound changed the interaction network, demonstrating that microbial interactions are indeed dynamic and responsive to local chemical context. PMID:28319121

Influence of metabolism in skin on dosimetry after topical exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bronaugh, R.L.; Collier, S.W.; Macpherson, S.E.

1994-12-01

Metabolism of chemicals occurs in skin and therefore should be taken into account when one determines topical exposure dose. Skin metabolism is difficult to measure in vivo because biological specimens may also contain metabolites from other tissues. Metabolism in skin during percutaneous absorption can be studied with viable skin in flow-through diffusion cells. Several compounds metabolized by microsomal enzymes in skin (benzo[a]pyrene and 7-ethoxycoumarin) penetrated human and hairless guinea pig skin predominantly unmetabolized. However, compounds containing a primary amino group (p-aminobenzoic acid, benzocaine, and azo color reduction products) were substrates for acetyltransferase activity in skin and were substantially metabolized duringmore » absorption. A physiologically based pharmacokinetic model has been developed with an input equation, allowing modeling after topical exposure. 14 refs., 3 figs., 4 tabs.« less

Air pollution and rural biomass fuels in developing countries: A pilot village study in India and implications for research and policy

NASA Astrophysics Data System (ADS)

Smith, Kirk R.; Aggarwal, A. L.; Dave ^✠, R. M.

The results of a pilot study in four Indian villages of personal exposure to total suspended particulates (TSP) and particulate benzo(a)pyrene (BaP) of women cooking on simple stoves using traditional biomass fuels are presented together with socioeconomic and fuel-use determinations. TSP exposures averaged nearly 7 mg m -3 and BaP about 4000 ng m -3 during the cooking period which occupied 10% of the year. The factors affecting indoor air pollution exposures in rural areas of developing countries are categorized and discussed by reference to the few published field measurements. Comparisons are made with other common exposures in urban and occupational settings. The sparse information indicates that rural exposures are relatively high. Subjects for future research are outlined and general policy implications mentioned.

Soils impacted by PAHs: Would the stabilized organic matter be a green tool for the immobilization of these noxious compounds?

PubMed

Dores-Silva, Paulo R; Cotta, Jussara A O; Landgraf, Maria D; Rezende, Maria O O

2018-05-04

The objective of this study was to investigate the role of stabilized organic matter (vermicompost) and tropical soils in the sorption of naphthalene, anthracene and benzo[a]pyrene. The results obtained for the three compounds were extrapolated for the priority polycyclic aromatic hydrocarbons (PAHs) pollutants according to Environmental Protection Agency (US EPA). To evaluate the sorption process, high performance liquid chromatography was employed and the data was fitted by Freundlich isotherms. The results suggest that the sorption effect generally increases with the number of benzene rings of the PAHs, and that the persistence of PAHs in the environment is possibly related to the number of benzene rings in the PAH molecule. In addition, the pH of the vermicompost can strongly affect the adsorption process in this matrix.

Creosote released from railway-ties recycled and the sanitary risks.

PubMed

Zicari, Giuseppe; Allegro, Giuseppe; Russo, Domenico; Rivetti, Daniela; Soardo, Vincenzo; Cerrato, Elena

2013-01-01

Through the history of railways, wooden crossties impregnated with potentially hazardous creosote tar, have been used for years. There are six major classes of compounds in the creosote: aromatic hydrocarbons; tar acids/phenolics; tar bases/nitrogen-containing heterocycles; aromatic amines; sulfur-containing heterocycles; and oxygen-containing heterocycles. The creosote molecules applied in railway crossties can be released in the environment and they can bioaccumulate in animals and vegetables. Some constituents (benzo(a)pyrene and phenolics like benzene) are considered as being carcinogenic which renders the entire complex of creosote to be classified as potentially carcinogenic. After several decades of use the railway-ties are been recycled for varies uses like fences, stakes for agriculture and fruit production or bank protection. In this paper are examined some environmental and sanitary risks from wood impregnated with creosote reported in the literature.

Airborne Measurements of atmospheric PAH's across Europe

NASA Astrophysics Data System (ADS)

Davison, B.; Jaward, F.; Jones, K.; Lee, R.

2003-04-01

Atmospheric measurements of PAHs were taken aboard the DRL Falcon 20 during May 2001. A sampling system was designed to work aboard this aircraft platform. Particulate PAHs were collected on a glass fiber filter (GFF) with their gaseous component concentrated on a polyurethane foam sheets located behind the filter. Typically sampling volumes of between 20-50m^3 were collected which equated to a collection time of about 30minutes. In this way the distance travelled was kept within an acceptable level, about 60 nautical miles. The average concentrations of the data set for phenanthrene was 450 pg m-3 while values for many of the heavier PAH marker compounds used in the UK such as benzo(a)pyrene, diben(ah)anthracene were below the detection limits on all flights. The results will be discussed with consideration of location, altitude and airmass trajectory.

Hepatic effects of orally administered styrene in rats.

PubMed

Srivastava, S P; Das, M; Mushtaq, M; Chandra, S V; Seth, P K

1982-08-01

Adult male rats receiving styrene by gavage (200 or 400 mg kg-1, 6 days a week) for 100 days exhibited a significant dose-dependent increase in hepatic benzo[a]pyrene hydroxylase and aminopyrine-N-demethylase, a decrease in glutathione-S-transferase and no change in glucose-6-phosphatase. A decrease in the activity of mitochondrial succinic dehydrogenase and beta-glucuronidase was also observed. Activity of acid phosphatase was decreased only at the higher dose level. Levels of serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were elevated only at the higher dose level. The absolute and relative weights of the liver of control and treated animals showed no significant difference. Histopathological studies of the liver tissue revealed tiny areas of focal necrosis, consisting of few degenerated hepatocytes and inflammatory cells at the higher dose level only.

Risk assessment of drinking water in a reservoir contaminated by PAH's originated from road traffic.

PubMed

Ishimaru, T; Inouye, H; Morioka, T

1990-04-01

The loads of Polycyclic Aromatic Hydrocarbons (PAHs) originating from road traffic were measured and in units of per vehicle per meter was estimated as follows: 0.07 ng/veh.m for Benzo[a]pyrene, and 0.83 ng/veh.m for Dibenzanthracene and so on, and 5.77 ng/veh.m for total PAHs. This unit is applied to risk estimation of drinking water in a reservoir where it is planned to construct a new high way the near future, and the concentration in the reservoir water is estimated to be 3.3-101 ng/l for individual PAH's. Assuming standard oral exposure to PAHs in raw water for drinking water supply, the estimated lifetime risk of carcinogenesis was less than 1 in 10(6), which is not considered significant.

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.

Meat consumption, cooking methods, mutagens, and risk of squamous cell carcinoma of the esophagus: a case-control study in Uruguay.

PubMed

De Stefani, Eduardo; Deneo-Pellegrini, Hugo; Ronco, Alvaro L; Boffetta, Paolo; Correa, Pelayo; Aune, Dagfinn; Mendilaharsu, María; Acosta, Gisele; Silva, Cecilia; Landó, Gabriel; Luaces, María E

2012-01-01

The role of meat in squamous cell carcinoma of the esophagus (ESCC) has been considered conflictive. For this reason, we decided to conduct a case-control study on meat consumption and ESCC. Data included 234 newly diagnosed and microscopically examined ESCC and 2,020 controls with conditions not related to tobacco smoking nor alcohol drinking and without changes in their diets. We studied total meat, red meat, beef, lamb, processed meat, poultry, fish, total white meat, liver, fried meat, barbecued meat, boiled meat, heterocyclic amines, nitrosodimethylamine, and benzo[a]pyrene in relation with the risk of ESCC. Red meat, lamb, and boiled meat were directly associated with the risk of ESCC, whereas total white meat, poultry, fish, and liver were mainly protective against this malignancy.

Approach to the characterization of the airborne organic matter (benzene soluble) in the atmosphere of Mexico City

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bravo, H.; Baez, A.P.

1961-01-01

Three areas of Mexico City were chosen from which to obtain samples of aromatic airborne particles. The samples were analyzed in order to have a broad idea of the composition of the material. The downtown area contained the highest concentration of organic benzene soluble material in the airborne particles, with the highest concentrations during the winter months. A combined sample (Ciudad Universitaria and Tacuba) was analyzed and gave the following figures of benzene soluble material in mg/g: fluoranthene - 160; pyrene - 210; benzo(a)anthracene - 47; benzo(a)pyrene - 82; benzo(e)pyrene - 150; benzo(g,h,i)perylene - 340; coronene - 160. A moremore » complete study is recommended in order to establish the actual parameters of the organic content in Mexico City's atmosphere.« less

Excitation-emission matrix fluorescence spectroscopy in conjunction with multiway analysis for PAH detection in complex matrices.

PubMed

Nahorniak, Michelle L; Booksh, Karl S

2006-12-01

A field portable, single exposure excitation-emission matrix (EEM) fluorometer has been constructed and used in conjunction with parallel factor analysis (PARAFAC) to determine the sub part per billion (ppb) concentrations of several aqueous polycyclic aromatic hydrocarbons (PAHs), such as benzo(k)fluoranthene and benzo(a)pyrene, in various matrices including aqueous motor oil extract and asphalt leachate. Multiway methods like PARAFAC are essential to resolve the analyte signature from the ubiquitous background in environmental samples. With multiway data and PARAFAC analysis it is shown that reliable concentration determinations can be achieved with minimal standards in spite of the large convoluting fluorescence background signal. Thus, rapid fieldable EEM analyses may prove to be a good screening method for tracking pollutants and prioritizing sampling and analysis by more complete but time consuming and labor intensive EPA methods.

Development and certification of a coal fly ash certified reference material for selected polycyclic aromatic hydrocarbons.

PubMed

Cao, X; Xu, X; Cui, W; Xi, Z

2001-08-01

The development and certification of a coal fly ash certified reference material (CRM) for polycyclic aromatic hydrocarbons (PAH) is described; this is the first natural matrix CRM for organic environmental analysis in China. The homogeneity and stability of this material have been tested by HPLC. The concentrations of several PAH were determined by use of two independent, different methods--solvent extraction-HPLC analysis with UV detection coupled with fluorescence detection (FLD) and solvent extraction, isolation with a silica column, and GC analysis with flame ionization detection (FID). Five certified values were determined: phenanthrene 7.1 +/- 2.6 microg g(-1), anthracene 2.0 +/- 0.8 microg g(-1), fluoranthene 7.4 +/- 1.9 microg g(-1), pyrene 7 +/- 2 microg g(-1), and benzo[a]pyrene 1.3 +/- 0.3 microg g(-1). Reference values for several other PAH are also suggested.

Semi-volatile organic compounds and trace elements in the Yangtze River source of drinking water.

PubMed

Wu, Bing; Zhang, Xuxiang; Zhang, Xiaolin; Yasun, Aishangjiang; Zhang, Yan; Zhao, Dayong; Ford, Tim; Cheng, Shupei

2009-08-01

Determination of 24 semi-volatile organic compounds (SVOCs) and 24 trace elements in water samples was conducted in order to investigate the quality of the Nanjing source of drinking water taken from Yangtze River. The total concentrations of SVOCs and trace elements were in the range of 1,951-11,098 ng/l and 51,274-72,384 microg/l, respectively. No significant seasonal changes were found for the pollutants' concentrations. A primary health risk assessment was carried out to evaluate potential health effects. Risk quotients involving carcinogenic effects for benzo(a)anthracene, benzo(a)pyrene, benzo(b)fluoranthene, dibenz(a,h)anthracene, bis(2-ethylhexyl)phthalate and arsenic were >1 under the worst-case scenario. The results of this study demonstrate the importance of further studies on the environmental health effects of exposure to the source water.

Cancer Risks in Aluminum Reduction Plant Workers

PubMed Central

Labrèche, France

2014-01-01

Objective and Methods: This review examines epidemiological evidence relating to cancers in the primary aluminum industry where most of what is known relates to Söderberg operations or to mixed Söderberg/prebake operations. Results and Conclusions: Increased lung and bladder cancer risks have been reported in Söderberg workers from several countries, but not in all. After adjustment for smoking, these cancer risks still increase with cumulative exposure to benzo(a)pyrene, used as an index of coal tar pitch volatiles exposure. Limited evidence has been gathered in several cohorts for an increased risk of tumors at other sites, including stomach, pancreas, rectum/rectosigmoid junction, larynx, buccal cavity/pharynx, kidney, brain/nervous system, prostate, and lymphatic/hematopoietic tissues (in particular non-Hodgkin lymphoma, Hodgkin disease, and leukemia). Nevertheless, for most of these tumor sites, the relationship with specific exposures has not been demonstrated clearly and further follow-up of workers is warranted. PMID:24806725

Acute biotoxic effect of styrene on rat liver. Correlation with enzyme-mediated mutagenicity of benzpyrene and acrylonitrile.

PubMed

Roberfroid, M; Poncelet, F; Lambotte-Vandepaer, M; Duverger-Van Bogaert, M; de Meester, C; Mercier, M

1978-01-01

Styrene is commonly used in western Europe for the manufacture of plastics suitable for packaging foodstuffs. This report demonstrates that, injected intraperitoneally at a dose as low as 10 mg/kg, styrene modifies the catalytic properties of aryl hydrocarbon hydroxylase by reducing its KM value. A similar effect is reported for two potent chemical carcinogens, 3-methylcholanthrene and benzo(a)pyrene. Ethylbenzene and benzo(e)pyrene and phenobarbital do not produce the same effect. Pretreatments of the rats with chemicals which modify aryl hydrocarbon hydroxylase also increase the capacity of the liver enzymes to activate benzopyrene to a mutagenic intermediate in vitro, as measured by the Ames test for mutagenicity. Exposure to both styrene and the other modifiers of the xenobiotic-metabolizing enzymes could thus influence the carcinogenic and toxic effects of chemicals which are activated by these enzymes. This hypothesis needs further investigation.

Polycyclic Aromatic Hydrocarbons in Electrocautery Smoke during Peritonectomy Procedures

PubMed Central

Näslund Andréasson, Sara; Mahteme, Haile; Sahlberg, Bo; Anundi, Helena

2012-01-01

Objective. This study identified and quantified polycyclic aromatic hydrocarbons (PAHs) in electrocautery smoke during 40 peritonectomy procedures and investigated any correlations and/or differences between levels of PAHs and perioperative variables. Methods. PAHs were measured in personal and stationary sampling by 40 mm Millipore cassettes, for adsorption of both gaseous and particle-bound PAHs. Results. All 16 USEPA priority pollutant PAHs were detected during peritonectomy procedures, naphthalene being the most abundant. For the only two PAHs with Swedish occupational exposure limits (OELs), benzo[a]pyrene and naphthalene, limits were never exceeded. Amount of bleeding was the only perioperative variable that correlated with levels of PAHs. Conclusions. Low levels of PAHs were detected in electrocautery smoke during peritonectomy procedures, and an increased amount of bleeding correlated with higher levels of PAHs. For evaluation of long-term health effects, more studies are needed. PMID:22685482

[Effect of epsilon-aminocaproic acid, cyclophosphamide and their combination on the growth of autochthonous sarcomas of mice induced by benzo(a)pyrene].

PubMed

Anikin, I V; Tyndyk, M L; Zabezhinskiĭ, M A; Popovich, I G; Anisimov, V N; Pliss, G B

2014-01-01

Antifibrinolytic drug epsilon-aminocaproic acid as a therapeutic form (5% solution in saline) was tested for antitumor activity in the autochthonous subcutaneous tumors of mice, induced by benzo (a) pyrene, in monotherapy mode (instead animals received drinking water) and in combination with cyclophosphamide, which was administered once intraperitoneally in the dose of 200 mg/kg. In the control groups, treated with drinking water and saline solution instead of water, there was no stabilization and reduction in tumor volume, while in the groups receiving epsilon-aminocaproic acid, cyclophosphamide and their combination statistically significantly in comparison with the control groups there was increased the proportion of tumors with not changed or reduced volume; epsilon-aminocaproic acid enhanced the antitumor effect of cyclophosphamide. The data obtained are for further study of the antitumor effect of epsilon-aminocaproic acid.

Unscheduled DNA synthesis in human bronchial epithelium treated with various chemical carcinogens in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishikawa, T.; Ide, F.; Kodama, K.

1984-07-01

A system was developed in which organ culture of human bronchial epithelium was used in combination with autoradiography for quantitative measurement of unscheduled DNA synthesis (UDS) in bronchial epithelial cells. Human bronchi obtained at surgery were cut into small sections and treated with various carcinogens plus (methyl-/sup 3/H)thymidine in short-term organ culture. Significant numbers of silver grains, indicating UDS, were detected on the nuclei of epithelial cells of human bronchi treated with carcinogens, and the numbers were proportional to the concentrations of carcinogens. In this system seven representative carcinogens induced UDS. Four active metabolites of benzo(a)pyrene, and benz(a)anthracene also weremore » found to induce very active UDS in human bronchial epithelium. These findings suggest that human bronchial epithelial cells can repair different types of DNA modification induced by chemical carcinogens.« less

Carcinogens induce reversion of the mouse pink-eyed unstable mutation

PubMed Central

Schiestl, Robert H.; Aubrecht, Jiri; Khogali, Fathia; Carls, Nicholas

1997-01-01

Deletions and other genome rearrangements are associated with carcinogenesis and inheritable diseases. The pink-eyed unstable (pun) mutation in the mouse is caused by duplication of a 70-kb internal fragment of the p gene. Spontaneous reversion events in homozygous pun/pun mice occur through deletion of a duplicated sequence. Reversion events in premelanocytes in the mouse embryo detected as black spots on the gray fur of the offspring were inducible by the carcinogen x-rays, ethyl methanesulfonate, methyl methanesulfonate, ethyl nitrosourea, benzo[a]pyrene, trichloroethylene, benzene, and sodium arsenate. The latter three carcinogens are not detectable with several in vitro or in vivo mutagenesis assays. We studied the molecular mechanism of the carcinogen-induced reversion events by cDNA analysis using reverse transcriptase–PCR method and identified the induced reversion events as deletions. DNA deletion assays may be sensitive indicators for carcinogen exposure. PMID:9114032

DNA and proteins of the nuclear matrix are the main targets of benzo[a]pyrene's action in rat hepatocytes.

PubMed

Widłak, P; Rzeszowska-Wolny, J

1993-01-01

The binding of [14C]benzo[a]pyrene (B[a]P) to DNA and proteins in total nuclei and subnuclear fractions of cultured rat hepatocytes was compared. The main targets of B[a]P were non-histone high molecular weight proteins of the nuclear matrix and DNA sequences attached to this structure. Following 24 h exposure to B[a]P the amounts of adducts in the nuclear matrix DNA and proteins were twice as high as in total nuclei. After withdrawal of the carcinogen containing medium the level of B[a]P-induced adducts gradually decreased but always remained the highest in the nuclear matrix proteins. Removal of adducts from the nuclear matrix DNA was more efficient than from the other DNA fractions, and 72 h after exposure to the carcinogen the level of DNA adducts in this fraction was similar to that in total nuclei.

Assessment of genotoxic exposure in Swedish coke-oven work by different methods of biological monitoring.

PubMed

Reuterwall, C; Aringer, L; Elinder, C G; Rannug, A; Levin, J O; Juringe, L; Onfelt, A

1991-04-01

This study evaluated the results of several biological methods used simultaneously to monitor coke-oven work. Blood samples from 44 male coke-oven workers and 48 male referents, matched for age and smoking/snuff consumption, were examined for cytogenetic damage in lymphocytes. Urinary thioether excretion was determined for 62, and urine mutagenicity for 31, of the subjects, who followed a standardized diet during the urine sampling. Exposure to polycyclic aromatic hydrocarbons varied with work task, the ambient air levels of benzo[a]pyrene sometimes exceeding 5 micrograms/m3. Cytogenetic damage, urine mutagenicity, and thioether excretion did not differ between the groups. The smokers, however, had significantly higher sister chromatid exchange frequencies, urine mutagenicity, and thioether excretion than the nonsmokers. The absence of biological indications of genotoxic exposure was unexpected and indicates that the studied methods are not adequate to assess the carcinogenic risks of Swedish coke-oven workers.

Use of constant wavelength synchronous spectrofluorimetry for identification of polycyclic aromatic hydrocarbons in air particulate samples

NASA Astrophysics Data System (ADS)

Sharma, Homdutt; Jain, V. K.; Khan, Zahid H.

2013-05-01

We have developed a simple, rapid, inexpensive method for the identification of fluoranthene (Flan), benz(a)anthracene (BaA), benzo(a)pyrene (BaP), benzo(k)fluoranthene (BkF), pyrene (Pyr), benz(ghi)perylene (BghiP) in suspended particulate matter in an urban environment of Delhi. Suspended particulate matter samples of 24 h duration were collected on glass fiber filter papers. Polycyclic aromatic hydrocarbons (PAHs) were extracted from the filter papers using dichloromethane (DCM) and hexane with ultrasonication method. Comparison of the characteristic emission of spectra of PAHs with standard spectra indicated the degree of condensation of aromatic compounds present in investigated mixtures. It was also possible to identify some individual compounds. However, this identification could be more effective with the use of the respective values of Δλ parameter for each particular component of the mixture.

Direct photolysis of polycyclic aromatic hydrocarbons in drinking water sources.

PubMed

Sanches, S; Leitão, C; Penetra, A; Cardoso, V V; Ferreira, E; Benoliel, M J; Crespo, M T Barreto; Pereira, V J

2011-09-15

The widely used low pressure lamps were tested in terms of their efficiency to degrade polycyclic aromatic hydrocarbons listed as priority pollutants by the European Water Framework Directive and the U.S. Environmental Protection Agency, in water matrices with very different compositions (laboratory grade water, groundwater, and surface water). Using a UV fluence of 1500 mJ/cm(2), anthracene and benzo(a)pyrene were efficiently degraded, with much higher percent removals obtained when present in groundwater (83-93%) compared to surface water (36-48%). The removal percentages obtained for fluoranthene were lower and ranged from 13 to 54% in the different water matrices tested. Several parameters that influence the direct photolysis of polycyclic aromatic hydrocarbons were determined and their photolysis by-products were identified by mass spectrometry. The formation of photolysis by-products was found to be highly dependent on the source waters tested. Copyright © 2011 Elsevier B.V. All rights reserved.

Antigenotoxic potential of certain dietary constituents.

PubMed

Shukla, Yogeshwer; Arora, Annu; Taneja, Pankaj

2003-01-01

The human diet contains a variety of compounds that exhibit chemopreventive effects towards an array of xenobiotics. In the present study, the antigenotoxic potential of selected dietary constituents including Diallyl sulfide (DAS), Indole-3-carbinol (I3C), Curcumin (CUR), and Black tea polyphenols (BTP) has been evaluated in the Salmonella typhimurium reverse mutation and mammalian in vivo cytogenetic assays. In addition, the anticlastogenic effect of the above dietary constituents was identified towards Benzo(a)pyrene (BaP) and cyclophosphamide- (CP) induced cytogenetic damage in mouse bone marrow cells. The induction of BaP and CP induced chromosomal aberrations, micronuclei formation, and sister chromatid exchanges (SCEs) were found to be inhibited in a dose-dependent manner by DAS, I3C, CUR, and BTP. Thus the study reveals the antimutagenic potential of these dietary compounds towards BaP- and CP-induced genotoxicity in microbial and mammalian test systems. Copyright 2003 Wiley-Liss, Inc.

Antimutagenic and anticarcinogenic effects of betel leaf extract against the tobacco-specific nitrosamine 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK).

PubMed

Bhide, S V; Padma, P R; Amonkar, A J

1991-01-01

Earlier studies showed that betel leaf inhibits the mutagenic action of standard mutagens like benzo[a]pyrene and dimethylbenz[a]anthracene. Since tobacco-specific nitrosamines are the major carcinogens present in unburnt forms of tobacco, we studied the effect of an extract of betel leaf on the mutagenic and carcinogenic actions of one of the most potent, 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). Betel-leaf extract and hydroxychavicol suppressed the mutagenicity of NNK in both the Ames and the micronucleus test. In studies in mice, betel-leaf extract reduced the tumorigenic effects of NNK by 25%. Concurrent treatment with the extract also inhibited the decreases in levels of vitamin A in liver and plasma induced by NNK. Betel leaf thus has protective effects against the mutagenic, carcinogenic and adverse metabolic effects of NNK in mice.

Proteomic characterization of the outer membrane vesicle of the halophilic marine bacterium Novosphingobium pentaromativorans US6-1.

PubMed

Yun, Sung Ho; Lee, Sang-Yeop; Choi, Chi-Won; Lee, Hayoung; Ro, Hyun-Joo; Jun, Sangmi; Kwon, Yong Min; Kwon, Kae Kyoung; Kim, Sang-Jin; Kim, Gun-Hwa; Kim, Seung Il

2017-01-01

Novosphingobium pentaromativorans US6-1 is a Gram-negative halophilic marine bacterium able to utilize several polycyclic aromatic hydrocarbons such as phenanthrene, pyrene, and benzo[a]pyrene. In this study, using transmission electron microscopy, we confirmed that N. pentaromativorans US6-1 produces outer membrane vesicles (OMVs). N. pentaromativorans OMVs (hereafter OMV Novo ) are spherical in shape, and the average diameter of OMV Novo is 25-70 nm. Proteomic analysis revealed that outer membrane proteins and periplasmic proteins of N. pentaromativorans are the major protein components of OMV Novo . Comparative proteomic analysis with the membrane-associated protein fraction and correlation analysis demonstrated that the outer membrane proteins of OMV Novo originated from the membrane- associated protein fraction. To the best of our knowledge, this study is the first to characterize OMV purified from halophilic marine bacteria.

Solid-state surface luminescence of polycyclic aromatic hydrocarbons adsorbed on cellulose diacetate matrices

NASA Astrophysics Data System (ADS)

Rogacheva, Svetlana M.; Shipovskaya, Anna B.; Volkova, Elena V.; Khurshudyan, Grachia N.; Suska-Malawska, Malgorzata; Gubina, Tamara I.

2018-04-01

The spectral-kinetic characteristics of luminescence of 17 polycyclic aromatic hydrocarbons (PAH) sorbed from a "water-organic solvent" medium on cellulose diacetate (CDA) matrices were studied. A significant increase in the fluorescence signal on the CDA matrix was observed for 13 PAHs in comparison with aqueous solutions. The highest detection sensitivity was found for pyrene, benzo(a)pyrene, and benzo(k)fluoranthene. The fluorescence spectra of two PAH indicator pairs (anthracene-phenanthrene and pyrene-fluoranthene) used to control toxicant emission sources were studied with the simultaneous presence of isomers in the analyte, depending on the excitation wavelength. For both isomer pairs, it has been found that the spectra of their solid-state luminescence overlap insignificantly, the characteristic peaks do not coincide and do not overlap, the sensitivities of detection are close to each other, which makes it possible to consider this technique as promising to control PAH contamination sources.

Benzo(a)pyrene-induced cytochrome p4501A expression of four freshwater fishes (Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus).

PubMed

Lee, Jin Wuk; Yoon, Hong-Gil; Lee, Sung Kyu

2015-05-01

Oryzias latipes, Danio rerio, Cyprinus carpio, and Zacco platypus are useful indicator species for CYP1A biomarker studies; however, comparative studies have not been performed. To compare susceptibility, dose- and time-dependent CYP1A induction at the mRNA and protein levels in response to benzo(a)pyrene (BaP) exposure was analyzed. At the mRNA level, a statistically significant difference was found among the four species; however, such was not observed at the protein level. C. carpio showed the highest CYP1A induction level and the steepest slope in the dose-response curve. To assess susceptibility, the difference in CYP1A mRNA induction among species must be considered, and C. carpio was the most sensitive species of the four evaluated in terms of CYP1A expression. Copyright © 2015 Elsevier B.V. All rights reserved.

Developmental toxicity of p,p'-dichlorodiphenyltrichloroethane, 2,4,6-trinitrotoluene, their metabolites, and benzo[a]pyrene in Xenopus laevis embryos.

PubMed

Saka, Masahiro

2004-04-01

Since 1995, high incidences of deformed frogs have been documented in Kitakyushu, Japan. In this area, relatively high concentrations of DDT, trinitrotoluene (TNT), their metabolites (p,p'-dichlorodiphenyldichloroethylene [DDE], p,p'-dichlorodiphenyldichloroethane [DDD], 2-amino-4,6-dinitrotoluene [2ADNT], and 4-amino-2,6-dinitrotoluene [4ADNT]), and benzo[a]pyrene [BaP]) have been identified from field samples. I used a standardized assay with Xenopus laevis embryos (frog embryo teratogenesis assay--Xenopus, FETAX) to examine the developmental toxicity of these compounds. Both DDE and BaP were considered nearly nontoxic in embryonic development because they induced low (< 10%) mortality and malformation incidence even at the highest concentrations tested (DDE, 393 microM; BaP, 13.2 microM). The DDD (96-h median lethal concentration [LC50] = 44.1 microM, 96-h median effective concentration [EC50] for malformation = 14.9 microM) was more lethal and teratogenic than its parent compound, DDT (96-h LC50 = 101 microM, 96-h EC50 = 41.5 microM). Predominant symptoms observed were axial malformations (DDT and DDD) and irregular gut coiling (DDT). However, DDT and DDD should not act as major lethal or teratogenic toxicants in the aquatic environment within a short-term exposure via water because their 96-h LC50 and 96-h EC50 values were extremely high, considering their low solubility in water. The TNT (96-h LC50 = 16.7 microM) was more lethal than 2ADNT (96-h LC50 = 166 microM) or 4ADNT (96-h LC50 = 115 microM). Although 4ADNT (96-h EC50 = 85.8 microM) induced various tadpole malformations, it was a weak teratogen compared with TNT (96-h EC50 = 9.78 microM) and 2ADNT (96-h EC50 = 16.9 microM). The most typical malformations observed were axial malformations, eye abnormalities (TNT), edema, and irregular gut coiling (2ADNT and 4ADNT). The 96-h LC50 and 96-h EC50 values of TNT, 2ADNT, and 4ADNT were lower than their saturated concentrations in water. Therefore, these nitroaromatic compounds may show lethal or teratogenic effects on aquatic animals if their habitats are severely contaminated with TNT.

Reduced cytochrome P4501A activity and recovery from oxidative stress during subchronic benzo[a]pyrene and benzo[e]pyrene treatment of rainbow trout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curtis, Lawrence R., E-mail: larry.curtis@oregonstate.edu; Garzon, Claudia B.; Arkoosh, Mary

2011-07-01

This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100 nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2 nM [{sup 3}H]2, 3, 7, 8-tetrachloro-dibenzo-p-dioxin from rainbow trout AHR2{alpha}. Based on appearance of fluorescent aromatic compounds in bile over 3, 7, 14, 28 or 50 days of feeding 3 {mu}g of BaP or BeP/g fish/day, rainbow trout liver readily excreted these polyaromatic hydrocarbons (PAHs) and their metabolites at near steady state rates. CYP1A proteins catalyzed more than 98% of ethoxyresorufin-O-deethylasemore » (EROD) activity in rainbow trout hepatic microsomes. EROD activity of hepatic microsomes initially increased and then decreased to control activities after 50 days of feeding both PAHs. Immunohistochemistry of liver confirmed CYP1A protein increased in fish fed both PAHs after 3 days and remained elevated for up to 28 days. Neither BaP nor BeP increased hepatic DNA adduct concentrations at any time up to 50 days of feeding these PAHs. Comet assays of blood cells demonstrated marked DNA damage after 14 days of feeding both PAHs that was not significant after 50 days. There was a strong positive correlation between hepatic EROD activity and DNA damage in blood cells over time for both PAHs. Neither CYP1A protein nor 3-nitrotyrosine (a biomarker for oxidative stress) immunostaining in trunk kidney were significantly altered by BaP or BeP after 3, 7, 14, or 28 days. There was no clear association between AHR2{alpha} affinity and BaP and BeP-induced oxidative stress. - Highlights: > No direct association between aryl hydrocarbon receptor affinity and polyaromatic hydrocarbon induced oxidative stress. > There was a strong correlation between cytochrome P4501A activity and oxidative stress as measured with the comet assay. > There was no correlation between cytochrome P4501A protein and oxidative stress as measured with the comet assay.« less

Further characterization of benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects.

PubMed

Bausinger, Julia; Schütz, Petra; Piberger, Ann Liza; Speit, Günter

2016-03-01

The present study aims to further characterize benzo[a]pyrene diol-epoxide (BPDE)-induced comet assay effects. Therefore, we measured DNA effects by the comet assay and adduct levels by high-performance liquid chromatography (HPLC) in human lymphocytes and A549 cells exposed to (±)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(±)-anti-BPDE] or (+)-anti-benzo[a]pyrene-7,8-diol 9,10-epoxide [(+)-anti-BPDE]. Both, the racemic form and (+)-anti-BPDE, which is the most relevant metabolite with regard to mutagenicity and carcinogenicity, induced DNA migration in cultured lymphocytes in the same range of concentrations to a similar extent in the alkaline comet assay after exposure for 2h. Nevertheless, (+)-anti-BPDE induced significantly enhanced DNA migration after 16 and 18h post-cultivation which was not seen in response to (±)-anti-BPDE. Combination of the comet assay with the Fpg (formamidopyrimidine-DNA glycosylase) protein did not enhance BPDE-induced effects and thus indicated the absence of Fpg-sensitive sites (oxidized purines, N7-guanine adducts, AP-sites). The aphidicolin (APC)-modified comet assay suggested significant excision repair activity of cultured lymphocytes during the first 18h of culture after a 2 h-exposure to BPDE. In contrast to these repair-related effects measured by the comet assay, HPLC analysis of stable adducts did not reveal any significant removal of (+)-anti-BPDE-induced adducts from lymphocytes during the first 22h of culture. On the other hand, HPLC measurements indicated that A549 cells repaired about 70% of (+)-anti-BPDE-induced DNA-adducts within 22h of release. However, various experiments with the APC-modified comet assay did not indicate significant repair activity during this period in A549 cells. The conflicting results obtained with the comet assay and the HPLC-based adduct analysis question the real cause for BPDE-induced DNA migration in the comet assay and the reliability of the APC-modified comet assay for the determination of DNA excision repair activity in response to BPDE in different cell types. © The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Benzo[a]pyrene affects Jurkat T cells in the activated state via the antioxidant response element dependent Nrf2 pathway leading to decreased IL-2 secretion and redirecting glutamine metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murugaiyan, Jayaseelan; Rockstroh, Maxie; Wagner, Juliane

2013-06-15

There is a clear evidence that environmental pollutants, such as benzo[a]pyrene (B[a]P), can have detrimental effects on the immune system, whereas the underlying mechanisms still remain elusive. Jurkat T cells share many properties with native T lymphocytes and therefore are an appropriate model to analyze the effects of environmental pollutants on T cells and their activation. Since environmental compounds frequently occur at low, not acute toxic concentrations, we analyzed the effects of two subtoxic concentrations, 50 nM and 5 μM, on non- and activated cells. B[a]P interferes directly with the stimulation process as proven by an altered IL-2 secretion. Furthermore,more » B[a]P exposure results in significant proteomic changes as shown by DIGE analysis. Pathway analysis revealed an involvement of the AhR independent Nrf2 pathway in the altered processes observed in unstimulated and stimulated cells. A participation of the Nrf2 pathway in the change of IL-2 secretion was confirmed by exposing cells to the Nrf2 activator tBHQ. tBHQ and 5 μM B[a]P caused similar alterations of IL-2 secretion and glutamine/glutamate metabolism. Moreover, the proteome changes in unstimulated cells point towards a modified regulation of the cytoskeleton and cellular stress response, which was proven by western blotting. Additionally, there is a strong evidence for alterations in metabolic pathways caused by B[a]P exposure in stimulated cells. Especially the glutamine/glutamate metabolism was indicated by proteome pathway analysis and validated by metabolite measurements. The detrimental effects were slightly enhanced in stimulated cells, suggesting that stimulated cells are more vulnerable to the environmental pollutant model compound B[a]P. - Highlights: • B[a]P affects the proteome of Jurkat T cells also at low concentrations. • Exposure to B[a]P (50 nM, 5 μM) did not change Jurkat T cell viability. • Both B[a]P concentrations altered the IL-2 secretion of stimulated cells. • 608 different protein spots of Jurkat T cells were quantified using 2-DE-DIGE. • Pathway analysis identified Nrf2 and AhR pathway as regulated.« less

Monitoring of environmental exposure to polycyclic aromatic hydrocarbons: a review.

PubMed

Srogi, K

2007-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds with two or more fused aromatic rings. They have a relatively low solubility in water, but are highly lipophilic. Most of the PAHs with low vapour pressure in the air are adsorbed on particles. When dissolved in water or adsorbed on particulate matter, PAHs can undergo photodecomposition when exposed to ultraviolet light from solar radiation. In the atmosphere, PAHs can react with pollutants such as ozone, nitrogen oxides and sulfur dioxide, yielding diones, nitro- and dinitro-PAHs, and sulfonic acids, respectively. PAHs may also be degraded by some microorganisms in the soil. PAHs are widespread environmental contaminants resulting from incomplete combustion of organic materials. The occurrence is largely a result of anthropogenic emissions such as fossil fuel-burning, motor vehicle, waste incinerator, oil refining, coke and asphalt production, and aluminum production, etc. PAHs have received increased attention in recent years in air pollution studies because some of these compounds are highly carcinogenic or mutagenic. Eight PAHs (Car-PAHs) typically considered as possible carcinogens are: benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene (B(a)P), dibenzo(a,h)anthracene, indeno(1,2,3-cd)pyrene and benzo(g,h,i)perylene. In particular, benzo(a)pyrene has been identified as being highly carcinogenic. The US Environmental Protection Agency (EPA) has promulgated 16 unsubstituted PAHs (EPA-PAH) as priority pollutants. Thus, exposure assessments of PAHs in the developing world are important. The scope of this review will be to give an overview of PAH concentrations in various environmental samples and to discuss the advantages and limitations of applying these parameters in the assessment of environmental risks in ecosystems and human health. As it well known, there is an increasing trend to use the behavior of pollutants (i.e. bioaccumulation) as well as pollution-induced biological and biochemical effects on human organisms to evaluate or predict the impact of chemicals on ecosystems. Emphasis in this review will, therefore, be placed on the use of bioaccumulation and biomarker responses in air, soil, water and food, as monitoring tools for the assessment of the risks and hazards of PAH concentrations for the ecosystem, as well as on its limitations.

Highly sensitive and selective surface plasmon resonance sensor for detection of sub-ppb levels of benzo[a]pyrene by indirect competitive immunoreaction method.

PubMed

Miura, Norio; Sasaki, Makoto; Gobi, K Vengatajalabathy; Kataoka, Chiwa; Shoyama, Yukihiro

2003-07-01

A surface plasmon resonance (SPR)-immunosensor for detection of benzo[a]pyrene (BaP) is developed by using a model BaP-hapten compound, BaP-bovine serum albumin conjugate (BaP-BSA), and an anti-BaP-BSA monoclonal antibody. BaP-BSA conjugate is immobilized on a gold thin-film sensor chip by means of simple physical adsorption. The number of BaP-hapten units in BaP-BSA conjugate is estimated to be 28 from the difference in molecular weight (MW) between BaP-BSA conjugate and BSA based on the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) measurement. Anti-BaP-BSA antibody on contact with the BaP-BSA conjugate immobilized sensor chip causes an increase in the incident angle of the sensor chip. Binding of anti-BaP-BSA antibody with surface-immobilized BaP-BSA conjugate is inhibited by the presence of BaP in analyte solution, because of the inhibition effect of BaP. The SPR immunosensor for BaP functioning with the indirect competitive immunoreaction of anti-BaP-BSA antibody between the analyte (BaP) in testing solution and the BaP-BSA conjugate immobilized on the sensor chip provides a rapid determination (response time: ca. 15 min) of BaP in the concentration range of 0.01-1000 ppb. The antibody anchored to the sensor chip by antigen-antibody binding is removed on treatment with a pepsin solution (pH 2.0) for few minutes. The SPR sensor chip is found to be reusable for more than 20 times with a little decrease (<7%) in the sensor response. Detection of BaP by direct competitive immunoreactions is also carried out by enzyme-linked immunosorbent assay (ELISA). The concentration of BaP could be determined as low as 0.01 ppb and 2 ppb using the SPR sensor and the ELISA method, respectively. The SPR sensor is found to detect BaP selectively in the presence of 2-hydroxybiphenyl (HBP); the incident angle shift of the SPR sensor for BaP is found to be same irrespective to the presence or the absence of a same concentration (as much as 30 ppb) of HBP together.

Effect of land use activities on PAH contamination in urban soils of Rawalpindi and Islamabad, Pakistan.

PubMed

Ud Din, Ikhtiar; Rashid, Audil; Mahmood, Tariq; Khalid, Azeem

2013-10-01

Urbanization can increase the vulnerability of soils to various types of contamination. Increased contamination of urban soils with polycyclic aromatic hydrocarbon (PAH) could relate to increased number of petrol pump stations and mechanical workshops-a phenomenon that needs to be constantly monitored. This study was undertaken to explore the soil PAH levels in Rawalpindi and Islamabad urban areas in relation to land use activities. Composite soil samples from petrol pump stations and mechanical workshops (n = 32) areas were evaluated for five PAHs--naphthalene, phenanthrene, pyrene, benzo[a]pyrene, and indeno(1,2,3-cd)pyrene-and compared with control area locations with minimum petroleum-related activity (n = 16). Surface samples up to 3 cm depth were collected and extraction of analytes was carried out using n-hexane and dichloromethane. Prior to running the samples, standards (100 μg ml(-1)) were run on HPLC to optimize signal to noise ratio using acetonitrile as mobile phase at a flow rate of 1.25 ml/min at 40 °C. Significant differences between petrol pump stations and mechanical workshop areas were observed for individual PAH as well as with control area soil samples. Naphthalene was found to be the most abundant PAH in soil, ranging from 2.47 to 24.36 mg kg(-1). Correlation between the benzo[a]pyrene (BaP) level in soil and the total PAH concentration (r = 0.82, P < 0.0001) revealed that BaP can be used as a potential marker for PAH pollution. A clear segregation between petrogenic and pyrogenic sources of contamination was observed when low molecular weight PAHs detected in soil was plotted against high molecular weight PAHs. The former source comprised lubricants and used engine oil found at mechanical workshops, whereas the latter could be mostly attributed to vehicular emission at petrol pumps. The results indicate that PAH contamination in urban areas of Rawalpindi and Islamabad has direct relevance with land use for petroleum activity. We conclude that in order to reduce the soil PAH exposure in urban environment, petrol pumps and mechanical workshops must be shifted to less densely populated areas because of their role as important point sources for PAH emission.

Overexpression of Catalase Enhances Benzo(a)pyrene Detoxification in Endothelial Microsomes.

PubMed

Yang, Fang; Yang, Hong; Ramesh, Aramandla; Goodwin, J Shawn; Okoro, Emmanuel U; Guo, ZhongMao

2016-01-01

We previously reported that overexpression of catalase upregulated xenobiotic- metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic reticulum (ER) is the most active organelle involved in BaP metabolism. To examine the involvement of ER in catalase-induced BaP detoxification, we compared the level and distribution of XMEs, and the profile of BaP intermediates in the microsomes of wild-type and catalase transgenic endothelial cells. Our data showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1, CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP). Treatment of wild-type MAECs with 1μM BaP for 2 h increased the expression of microsomal CYP1A1, 1B1 and NQO1 by ~300, 64 and 116%, respectively. However, the same treatment did not significantly alter the expression of EH1 and GSTP. Overexpression of catalase did not significantly increase EH1, but upregulated BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the distribution of each of these enzymes in the microsomes. In contrast to our previous report showing lower level of BaP phenols versus BaP diols/diones in the whole-cell, this report demonstrated that the sum of microsomal BaP phenolic metabolites were ~60% greater than that of the BaP diols/diones after exposure of microsomes to BaP. Overexpression of catalase reduced the concentrations of microsomal BaP phenols and diols/diones by ~45 and 95%, respectively. This process enhanced the ratio of BaP phenol versus diol/dione metabolites in a potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins, but not EH1 in the ER might be the mechanism by which overexpression of catalase reduces the levels of all the BaP metabolites, and enhances the ratio of BaP phenolic metabolites versus diol/diones in endothelial microsomes.

Cardiac toxicity of 5-ring polycyclic aromatic hydrocarbons is differentially dependent on the aryl hydrocarbon receptor 2 isoform during zebrafish development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Incardona, John P., E-mail: john.incardona@noaa.gov; Linbo, Tiffany L.; Scholz, Nathaniel L.

Petroleum-derived compounds, including polycyclic aromatic hydrocarbons (PAHs), commonly occur as complex mixtures in the environment. Recent studies using the zebrafish experimental model have shown that PAHs are toxic to the embryonic cardiovascular system, and that the severity and nature of this developmental cardiotoxicity varies by individual PAH. In the present study we characterize the toxicity of the relatively higher molecular weight 5-ring PAHs benzo[a]pyrene (BaP), benzo[e]pyrene (BeP), and benzo[k]fluoranthene (BkF). While all three compounds target the cardiovascular system, the underlying role of the ligand-activated aryl hydrocarbon receptor (AHR2) and the tissue-specific induction of the cytochrome p450 metabolic pathway (CYP1A) weremore » distinct for each. BaP exposure (40 {mu}M) produced AHR2-dependent bradycardia, pericardial edema, and myocardial CYP1A immunofluorescence. By contrast, BkF exposure (4-40 {mu}M) caused more severe pericardial edema, looping defects, and erythrocyte regurgitation through the atrioventricular valve that were AHR2-independent (i.e., absent myocardial or endocardial CYP1A induction). Lastly, exposure to BeP (40 {mu}M) yielded a low level of CYP1A+ signal in the vascular endothelium of the head and trunk, without evident toxic effects on cardiac function or morphogenesis. Combined with earlier work on 3- and 4-ring PAHs, our findings provide a more complete picture of how individual PAHs may drive the cardiotoxicity of mixtures in which they predominate. This will improve toxic injury assessments and risk assessments for wild fish populations that spawn in habitats altered by overlapping petroleum-related human impacts such as oil spills, urban stormwater runoff, or sediments contaminated by legacy industrial activities. -- Highlights: Black-Right-Pointing-Pointer PAH compounds with 5 rings in different arrangements caused differential tissue-specific patterns of CYP1A induction in zebrafish embryos. Black-Right-Pointing-Pointer These compounds produced differential cardiac developmental toxicity that did not strictly correlate with associated CYP1A induction. Black-Right-Pointing-Pointer Cardiotoxicity of benzo(a)pyrene was partially dependent on the AHR2 isoform, while benzo(k)fluoranthene cardiotoxicity was not. Black-Right-Pointing-Pointer Individual PAH compounds have distinct toxicokinetic pathways in fish embryos, and act through different toxic mechanisms.« less

Carcinogenicity of airborne combustion products observed in subcutaneous tissue and lungs of laboratory rodents.

PubMed Central

Pott, F; Stöber, W

1983-01-01

Most air pollution in West Germany is caused by combustion products. Particulate organic matter released by incomplete combustion is suspected to contribute to the "urban factor" of lung cancer frequency in urban-industrial centers. The carcinogenic potential of single components, groups of compounds and total source emissions of combustion processes was investigated in laboratory animals by subcutaneous injection, intratracheal instillation or inhalation. Tests by subcutaneous injection of condensates of automobile exhaust, extracts of coal furnace emissions and of airborne particles and different fractions of these extracts showed that the polycyclic aromatic hydrocarbons (PAH) with four to six benzene rings have the strongest experimental carcinogenicity. However, polar compounds (heterocyclic nitrogen-containing PAH, phenols, and others) also show remarkable carcinogenic potency. There were large differences between the dose-response relationships of several PAHs. In the subcutaneous tissue, benzo(a)pyrene and dibenz(a,h)anthracene are the most carcinogenic of the tested airborne PAHs. Furthermore, they can induce high tumor rates in the lung after subcutaneous injection in newborn mice and after intratracheal instillation of mice or hamsters. The tumor rate of benzo(a)pyrene did not further increase after simultaneous instillation of carbon black, but lead chloride may have a promoting effect. Far more than 100 PAHs are found in the urban atmosphere. However, because of the remarkable similarity of the PAH profiles in the examined samples, it may be sufficient to measure just a few stable PAHs in the urban air in order to facilitate an assessment of the carcinogenic potency of the PAH content in the atmosphere. To examine the carcinogenic or cocarcinogenic effects of gas and vapor emissions, studies with a two-phase model were carried out: phase 1 relates to the induction of a basic tumor rate in the lung by a well known carcinogen, while phase 2 is characterized by an inhalation of the substance under investigation. In an experiment with mice, the inhalation of a mixture of SO2 and NO2 seemed to increase the basic tumor rate induced by dibenz(a,h)anthracene. In a similar two-phase experiment conducted with hamsters, the inhalation of diesel exhaust (total exhaust as well as exhaust without particles) increased a basic tumor rate induced by diethyl nitrosamine. These experiments deserve confirmation before a detailed interpretation is attempted. PMID:6186480

Carcinogenicity of airborne combustion products observed in subcutaneous tissue and lungs of laboratory rodents.

PubMed

Pott, F; Stöber, W

1983-01-01

Most air pollution in West Germany is caused by combustion products. Particulate organic matter released by incomplete combustion is suspected to contribute to the "urban factor" of lung cancer frequency in urban-industrial centers. The carcinogenic potential of single components, groups of compounds and total source emissions of combustion processes was investigated in laboratory animals by subcutaneous injection, intratracheal instillation or inhalation. Tests by subcutaneous injection of condensates of automobile exhaust, extracts of coal furnace emissions and of airborne particles and different fractions of these extracts showed that the polycyclic aromatic hydrocarbons (PAH) with four to six benzene rings have the strongest experimental carcinogenicity. However, polar compounds (heterocyclic nitrogen-containing PAH, phenols, and others) also show remarkable carcinogenic potency. There were large differences between the dose-response relationships of several PAHs. In the subcutaneous tissue, benzo(a)pyrene and dibenz(a,h)anthracene are the most carcinogenic of the tested airborne PAHs. Furthermore, they can induce high tumor rates in the lung after subcutaneous injection in newborn mice and after intratracheal instillation of mice or hamsters. The tumor rate of benzo(a)pyrene did not further increase after simultaneous instillation of carbon black, but lead chloride may have a promoting effect. Far more than 100 PAHs are found in the urban atmosphere. However, because of the remarkable similarity of the PAH profiles in the examined samples, it may be sufficient to measure just a few stable PAHs in the urban air in order to facilitate an assessment of the carcinogenic potency of the PAH content in the atmosphere. To examine the carcinogenic or cocarcinogenic effects of gas and vapor emissions, studies with a two-phase model were carried out: phase 1 relates to the induction of a basic tumor rate in the lung by a well known carcinogen, while phase 2 is characterized by an inhalation of the substance under investigation. In an experiment with mice, the inhalation of a mixture of SO2 and NO2 seemed to increase the basic tumor rate induced by dibenz(a,h)anthracene. In a similar two-phase experiment conducted with hamsters, the inhalation of diesel exhaust (total exhaust as well as exhaust without particles) increased a basic tumor rate induced by diethyl nitrosamine. These experiments deserve confirmation before a detailed interpretation is attempted.

Improved efficiency of extraction of polycyclic aromatic hydrocarbons (PAHs) from the National Institute of Standards and Technology (NIST) Standard Reference Material Diesel Particulate Matter (SRM 2975) using accelerated solvent extraction.

PubMed

Masala, Silvia; Ahmed, Trifa; Bergvall, Christoffer; Westerholm, Roger

2011-12-01

The efficiency of extraction of polycyclic aromatic hydrocarbons (PAHs) with molecular masses of 252, 276, 278, 300, and 302 Da from standard reference material diesel particulate matter (SRM 2975) has been investigated using accelerated solvent extraction (ASE) with dichloromethane, toluene, methanol, and mixtures of toluene and methanol. Extraction of SRM 2975 using toluene/methanol (9:1, v/v) at maximum instrumental settings (200 °C, 20.7 MPa, and five extraction cycles) with 30-min extraction times resulted in the following elevations of the measured concentration when compared with the certified and reference concentrations reported by the National Institute of Standards and Technology (NIST): benzo[b]fluoranthene, 46%; benzo[k]fluoranthene, 137%; benzo[e]pyrene, 103%; benzo[a]pyrene, 1,570%; perylene, 37%; indeno[1,2,3-cd]pyrene, 41%; benzo[ghi]perylene, 163%; and coronene, 361%. The concentrations of the following PAHs were comparable to the reference values assigned by NIST: indeno[1,2,3-cd]fluoranthene, dibenz[a,h]anthracene, and picene. The measured concentration of dibenzo[a,e]-pyrene was lower than the information value reported by the NIST. The measured concentrations of other highly carcinogenic PAHs (dibenzo[a,l]pyrene, dibenzo[a,i]pyrene, and dibenzo[a,h]pyrene) in SRM 2975 are also reported. Comparison of measurements using the optimized ASE method and using similar conditions to those applied by the NIST for the assignment of PAH concentrations in SRM 2975 indicated that the higher values obtained in the present study were associated with more complete extraction of PAHs from the diesel particulate material. Re-extraction of the particulate samples demonstrated that the deuterated internal standards were more readily recovered than the native PAHs, which may explain the lower values reported by the NIST. The analytical results obtained in the study demonstrated that the efficient extraction of PAHs from SRM 2975 is a critical requirement for the accurate determination of PAHs with high molecular masses in this standard reference material and that the optimization of extraction conditions is essential to avoid underestimation of the PAH concentrations. The requirement is especially relevant to the human carcinogen benzo[a]pyrene, which is commonly used as an indicator of the carcinogenic risk presented by PAH mixtures.

Lack of contribution of covalent benzo[a]pyrene-7,8-quinone-DNA adducts in benzo[a]pyrene-induced mouse lung tumorigenesis.

PubMed

Nesnow, Stephen; Nelson, Garret; Padgett, William T; George, Michael H; Moore, Tanya; King, Leon C; Adams, Linda D; Ross, Jeffrey A

2010-07-30

Benzo[a]pyrene (B[a]P) is a potent human and rodent lung carcinogen. This activity has been ascribed in part to the formation of anti-trans-7,8-dihydroxy-7,8-dihydroB[a]P-9,10-epoxide (BPDE)-DNA adducts. Other carcinogenic mechanisms have been proposed: (1) the induction of apurinic sites from radical cation processes, and (2) the metabolic formation of B[a]P-7,8-quinone (BPQ) that can form covalent DNA adducts or reactive oxygen species which can damage DNA. The studies presented here sought to examine the role of stable BPQ-DNA adducts in B[a]P-induced mouse lung tumorigenesis. Male strain A/J mice were injected intraperitoneally once with BPQ or trans-7,8-dihydroxy-7,8-dihydroB[a]P (BP-7,8-diol) at 30, 10, 3, or 0mg/kg. Lungs and livers were harvested after 24h, the DNA extracted and subjected to (32)P-postlabeling analysis. Additional groups of mice were dosed once with BPQ or BP-7,8-diol each at 30 mg/kg and tissues harvested 48 and 72 h later, or with B[a]P (50mg/kg, a tumorigenic dose) and tissues harvested 72 h later. No BPQ or any other DNA adducts were observed in lung or liver tissues 24, 48, or 72 h after the treatment with 30 mg/kg BPQ. BP-7,8-diol gave BPDE-DNA adducts at all time points in both tissues and B[a]P treatment gave BPDE-DNA adducts in the lung. In each case, no BPQ-DNA adducts were detected. Mouse body weights significantly decreased over time after BPQ or BP-7,8-diol treatments suggesting that systemic toxicity was induced by both agents. Model studies with BPQ and N-acetylcysteine suggested that BPQ is rapidly inactivated by sulfhydryl-containing compounds and not available for DNA adduction. We conclude that under these treatment conditions BPQ does not form stable covalent DNA adducts in the lungs or livers of strain A/J mice, suggesting that stable BPQ-covalent adducts are not a part of the complex of mechanisms involved in B[a]P-induced mouse lung tumorigenesis. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Biological Monitoring of Occupational Exposure to Polycyclic Aromatic Hydrocarbons at an Electric Steel Foundry in Tunisia.

PubMed

Campo, Laura; Hanchi, Mariem; Olgiati, Luca; Polledri, Elisa; Consonni, Dario; Zrafi, Ines; Saidane-Mosbahi, Dalila; Fustinoni, Silvia

2016-07-01

Occupational exposures during iron and steel founding have been classified as carcinogenic to humans, and the exposure to polycyclic aromatic hydrocarbons (PAHs) in this industrial setting may contribute to cancer risk. The occupational exposure to PAHs was assessed in 93 male workers at an electric steel foundry in Tunisia by biomonitoring, with the aims of characterizing the excretion profile and investigating the influence of job title and personal characteristics on the biomarkers. Sixteen 2-6 ring unmetabolized PAHs (U-PAHs) and eight hydroxylated PAH metabolites (OHPAHs) were analyzed by gas chromatography-triple quadrupole tandem mass spectrometry and liquid chromatography triple quadrupole tandem mass spectrometry, respectively. Among U-PAHs, urinary naphthalene (U-NAP) was the most abundant compound (median level: 643ng l(-1)), followed by phenanthrene (U-PHE, 18.5ng l(-1)). Urinary benzo[a]pyrene (U-BaP) level was <0.30ng l(-1) Among OHPAHs, 2-hydroxynaphthalene (2-OHNAP) was the most abundant metabolite (2.27 µg l(-1)). Median 1-hydroxypyrene (1-OHPYR) was 0.52 µg l(-1) Significant correlations among urinary biomarkers were observed, with Pearson's r ranging from 0.177 to 0.626. 1-OHPYR was correlated to benzo[a]pyrene, but not to five- and six-rings PAHs. A multiple linear regression model showed that job title was a significant determinant for almost all U-PAHs. In particular, employees in the steel smelter workshop had higher levels of high-boiling U-PAHs and lower levels of low-boiling U-PAHs than those of workers with other job titles. Among OHPAHs, this model was significant only for naphthols and 1-hydroxyphenanthrene (1-OHPHE). Smoking status was a significant predictor for almost all biomarkers. Among all analytes, U-PHE and 1-OHPHE were the less affected by tobacco smoke, and they were significantly correlated with both low- and high-molecular-weight compounds, and their levels were related to job titles, so they could be proposed as suitable biomarkers of PAH exposure at steel foundries. Based on 1-OHPYR levels, our findings show that occupational exposure of these workers was similar to that reported in recent studies of electric steel foundry workers. The multianalytic approach is useful in revealing different exposure levels among job titles. © The Author 2016. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Effects of light on the cytotoxicity and genotoxicity of benzo(a)pyrene and an oil refinery effluent in the newt

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandez, M.; l`Haridon, J.

1994-12-31

The genotoxicity and/or toxicity of benzo(a)pyrene (BaP) were evaluated under different lighting conditions in larvae and embryos of the newt Pleurodeles waltl. Visible light alone, UVA alone, or BaP alone had no toxic effects on the larvae. Conversely, toxic effects were observed in animals exposed to BaP + daylight, or BaP + UVA. The genotoxicity of BaP (50 ppb) was halved by its previous exposure to UVA, and was abolished at the lowest concentration (12.5 ppb). In other experiments, the larvae were exposed alternatively to BaP or Irr BaP (18 hours in dark) and UVA (6 hr in water), everymore » day for 8 days. All animals that had accumulated non-irradiated BaP (50 ppb) showed signs of severe toxicity, and 90% died before the end of the test. On the other hand, irradiated BaP (50 ppb) was a 4-fold less toxic and half as genotoxic as non-irradiated BaP. In addition, exposure of the animals to UVA alone for 4 days prior to treatment with BaP did not affect the genotoxicity or toxicity of this hydrocarbon. In the dark, the embryotoxicity of BaP was markedly attenuated by the presence of the jelly coats. Although UVA alone did not affect growth of the embryos, the toxicity of BaP was enhanced by the combined action of the two agents together or in succession (BaP + UVA or BaP then UVA). Larvae were treated with an oil refinery effluent (EF). At 125 ml/l, EF was not found to be genotoxic in the dark. However, in animals exposed to both EF and UVA, there was a progressive increase in level of micronucleated erythrocytes with increasing duration of daily exposure to UVA. Moreover, the genotoxic potential of irradiated EF + UVA was systematically below that of non-irradiated EF + UVA for all durations of exposure to ultraviolet light. Irradiation of this type of effluent might help reduce its harmful effects on aquatic species. Our results also suggest that metabolic activation is not necessary for hydrocarbons to induce toxic effects. 51 refs., 5 tabs., 3 figs.« less

Assessing the impact of Benzo[a]pyrene on Marine Mussels: Application of a novel targeted low density microarray complementing classical biomarker responses

PubMed Central

Sforzini, Susanna; Arlt, Volker M.; Barranger, Audrey; Dallas, Lorna J.; Oliveri, Caterina; Aminot, Yann; Pacchioni, Beniamina; Millino, Caterina; Lanfranchi, Gerolamo; Readman, James W.; Moore, Michael N.; Viarengo, Aldo; Jha, Awadhesh N.

2017-01-01

Despite the increasing use of mussels in environmental monitoring and ecotoxicological studies, their genomes and gene functions have not been thoroughly explored. Several cDNA microarrays were recently proposed for Mytilus spp., but putatively identified partial transcripts have rendered the generation of robust transcriptional responses difficult in terms of pathway identification. We developed a new low density oligonucleotide microarray with 465 probes covering the same number of genes. Target genes were selected to cover most of the well-known biological processes in the stress response documented over the last decade in bivalve species at the cellular and tissue levels. Our new ‘STressREsponse Microarray’ (STREM) platform consists of eight sub-arrays with three replicates for each target in each sub-array. To assess the potential use of the new array, we tested the effect of the ubiquitous environmental pollutant benzo[a]pyrene (B[a]P) at 5, 50, and 100 μg/L on two target tissues, the gills and digestive gland, of Mytilus galloprovincialis exposed invivo for three days. Bioaccumulation of B[a]P was also determined demonstrating exposure in both tissues. In addition to the well-known effects of B[a]P on DNA metabolism and oxidative stress, the new array data provided clues about the implication of other biological processes, such as cytoskeleton, immune response, adhesion to substrate, and mitochondrial activities. Transcriptional data were confirmed using qRT-PCR. We further investigated cellular functions and possible alterations related to biological processes highlighted by the microarray data using oxidative stress biomarkers (Lipofuscin content) and the assessment of genotoxicity. DNA damage, as measured by the alkaline comet assay, increased as a function of dose.DNA adducts measurements using 32P-postlabeling method also showed the presence of bulky DNA adducts (i.e. dG-N2-BPDE). Lipofiscin content increased significantly in B[a]P exposed mussels. Immunohistochemical analysis of tubulin and actin showed changes in cytoskeleton organisation. Our results adopting an integrated approach confirmed that the combination of newly developed transcriptomic approcah, classical biomarkers along with chemical analysis of water and tissue samples should be considered for environmental bioimonitoring and ecotoxicological studies to obtain holistic information to assess the impact of contaminants on the biota. PMID:28651000

Assessment of polycyclic aromatic hydrocarbons (PAHs) contamination in surface soil of coal stockpile sites in South Kalimantan, Indonesia.

PubMed

Mizwar, Andy; Priatmadi, Bambang Joko; Abdi, Chairul; Trihadiningrum, Yulinah

2016-03-01

Concentrations, spatial distribution, and sources of 16 polycyclic aromatic hydrocarbons (PAHs), listed as priority pollutants by the United States Environmental Protection Agency (USEPA), were investigated in surface soils of three different coal stockpile, agricultural, and residential sites in South Kalimantan Province, Indonesia. Total PAHs concentration ranged from 4.69 to 22.67 mg kg(-1)-dw. PAHs concentrations in soil of coal stockpile sites were higher than those in agricultural and residential soil. A complex of petrogenic origin and pyrolytic sources was found within the study area, as suggested by the isomeric ratios of PAHs. The results of principal component analysis and multiple linear regressions (PCA/MLR) showed that three sources contributed to the PAHs in the study area, including biomass and coal combustion (48.46%), raw coal (35.49%), and vehicular emission (16.05%). The high value of total benzo[a]pyrene equivalent concentration (B[a]Peq) suggests that local residents are exposed to a high carcinogenic potential.

Health impacts of productive conservation in urban transportation. Tapcut technical memorandum No. 27

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rowe, M.D.; Crowther, M.A.

1982-01-01

The literature on health effects of transportation-related pollutants is reviewed and assesses potential health risks of selected energy conservation policies for transportation systems in three representative cities. The conservation policies assessed are specified in other reports. The assessment includes health risks from pollutants emitted by vehicles, from pollutants emitted by industries involved in vehicle manufacturing, and from occupational accidents related to vehicle manufacturing throughout the economic system. Estimated health risk is dominated by ozone and hydrocarbon (benzo(a)pyrene) exposure. Results indicate that health risks from urban transportation systems will either remain constant or decline between 1980 and 2000 under all policiesmore » assessed. No significant change is projected for health risks from toxicants produced in vehicle manufacturing or from risks of occupational accidents throughout the economic system. In general, policies that reduce energy consumption also reduce projected health risks, even when they promote new technologies having potentially significant differences in emission characteristics and manufacturing requirements.« less

Linking biochemical perturbations in tissues of the African catfish to the presence of polycyclic aromatic hydrocarbons in Ovia River, Niger Delta region.

PubMed

Obinaju, Blessing E; Graf, Carola; Halsall, Crispin; Martin, Francis L

2015-06-01

Petroleum hydrocarbons including polycyclic aromatic hydrocarbons (PAHs) are a pollution issue in the Niger Delta region due to oil industry activities. PAHs were measured in the water column of the Ovia River with concentrations ranging from 0.1 to 1055.6 ng L(-1). Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy detected alterations in tissues of the African catfish (Heterobranchus bidorsalis) from the region showed varying degrees of statistically significant (P<0.0001, P<0.001, P<0.05) changes to absorption band areas and shifts in centroid positions of peaks. Alteration patterns were similar to those induced by benzo[a]pyrene in MCF-7 cells. These findings have potential health implications for resident local communities as H. bidorsalis constitutes a key nutritional source. The study provides supporting evidence for the sensitivity of infrared spectroscopy in environmental studies and supports their potential application in biomonitoring. Copyright © 2015 Elsevier Ltd. All rights reserved.

A model compound study: the ecotoxicological evaluation of five organic contaminants employing a battery of marine bioassays.

PubMed

Macken, Ailbhe; Giltrap, Michelle; Foley, Barry; McGovern, Evin; McHugh, Brendan; Davoren, Maria

2008-06-01

This paper describes the ecotoxicological evaluation of five organic contaminants frequently detected in marine sediments (tributyltin, triphenyltin, benzo[a]pyrene, fluoranthene, and PCB 153) using three marine species (Vibrio fischeri, Tetraselmis suecica, and Tisbe battagliai). The sensitivity of each species varied for all compounds. The triorganotins were consistently the most toxic to all species. The applicability of each test system to assess the acute toxicity of environmental contaminants and their use in Toxicity Identification Evaluation (TIE) is discussed. Suitability of the Microtox and T. battagliai tests for employment in TIE studies were further assessed through spiking experiments with tributyltin. Results demonstrated that the most effective treatment to remove organotin toxicity from the sample was the C18 resin. The results of this study have important implications for risk assessment in estuarine and coastal waters in Ireland, where, at present the monitoring of sediment and water quality is predominantly reliant on chemical analysis alone.

Contrast in the Photoelectric Effect of Organic and Biochemical Surfaces

PubMed Central

Birrell, G. B.; Burke, C.; Dehlinger, P.; Griffith, O. H.

1973-01-01

The photoelectric effect can provide the physical basis for a new method of mapping organic and biological surfaces. The technique, photoelectron microscopy, is similar to fluorescence microscopy using incident ultraviolet light except that photoejected electrons form the image of the specimen surface. In this work the minimum wavelengths of incident light required to produce an image were determined for the molecules 3,6-bis(dimethylamino)acridine (acridine orange) (I), benzo[a]pyrene (II), N,N,N′,N′-tetraphenylbenzidine (III), and copper phthalocyanine (IV). The photoelectron image thresholds for these compounds are 220 (I), 215 (II), 220 (III), and 240 nm (IV), all ±5 nm. Contrast of I-IV with respect to typical protein, lipid, nucleic acid, and polysaccharide surfaces was examined over the wavelength range 240-180 nm. The low magnification micrographs exhibited bright areas corresponding to I-IV but dark regions for the biochemical surfaces. The high contrast suggests the feasibility of performing extrinsic photoelectron microscopy experiments through selective labeling of sites on biological surfaces. ImagesFIGURE 3 PMID:4704486

Induction of microsomal drug metabolism in man and in the rat by exposure to petroleum.

PubMed Central

Harman, A W; Frewin, D B; Priestly, B G

1981-01-01

To determine the effect of petroleum exposure on the activity of hepatic mixed function oxidase enzymes, salivary elimination kinetics of antipyrine were determined in 19 petrol station attendants and compared with 19 controls. Antipyrine half life in petrol station attendants was shorter than in controls. Microsomal preparations (10 000 x g supernatants) were prepared from six male Porton rats exposed to petrol vapour (5 ppm at an air flow rate of 41/min for eight hours a day for three weeks) and six control rats maintained under the same conditions without exposure to petrol vapour. The rates of oxidative metabolism of antipyrine, aminopyrine, ethylmorphine, aniline, and benzo(a)pyrene were all increased by more than 45% in the petrol-exposed rats. The results indicate that petrol vapour is a moderately potent inducer of mixed function oxidase activity in rats, and that occupational exposure to petroleum may result in enhanced microsomal drug metabolism. PMID:7470408

Crystal Structure and Antitumor Activity of the Novel Zwitterionic Complex of tri-n-Butyltin(IV) with 2-Thiobarbituric Acid

PubMed Central

Balas, Vasilios I.; Hadjikakou, Sotiris K.; Hadjiliadis, Nick; Kourkoumelis, Nikolaos; Light, Mark E.; Hursthouse, Mike; Metsios, Apostolos K.; Karkabounas, Spyros

2008-01-01

A novel tri-n-butyl(IV) derivative of 2-thiobarbituric acid (HTBA) of formula [(n-Bu)3Sn(TBA) H2O] (1) has been synthesized and characterized by elemental analysis and 119Sn-NMR and FT-IR spectroscopic techniques. The crystal structure of complex 1 has been determined by single crystal X-ray diffraction analysis at 120(2) K. The geometry around Sn(IV) is trigonal bipyramidal. Three n-butyl groups and one oxygen atom from a deprotonated 2-thiobarbituric ligand are bonded to the metal center. The geometry is completed with one oxygen from a water molecule. Compound 1 exhibits potent, in vitro, cytotoxicity against sarcoma cancer cells (mesenchymal tissue) from the Wistar rat, polycyclic aromatic hydrocarbons (PAH, benzo[a]pyrene) carcinogenesis. In addition, the inhibition caused by 1, in the rate of lipoxygenase (LOX) catalyzed oxidation reaction of linoleic acid to hyperoxolinoleic acid, has been also kinetically and theoretically studied. The results are compared to that of cisplatin. PMID:18401456

[Polycyclic aromatic hydrocarbons (PAHs) in herbs and fruit teas].

PubMed

Ciemniak, Artur

2005-01-01

Polycyclic aromatic hydrocarbons (PAHs) of which benzo[a]pyrene is the most commonly studied and measured, are fused - ring aromatic compounds formed in both natural and man made processes and are found widely distributed throughout the human environment. PAHs occur as contaminants in different food categories and beverages including water, vegetables, fruit, cereals, oils and fats, barbecued and smoked meat. The sources of PAHs in food are predominantly from environmental pollution and food processing. PAHs emissions from automobile traffic and industry activities were show to influence the PAHs levels in vegetables and fruits. The present study was carried out to determine levels of 16 basic PAHs in herbs and fruit teas. The method was based on the hexane extraction and cleaned up by florisil cartridge. The extracts were analysed by GC-MS. The levels of total PAHs varied from 48,27 microg/kg (hibiscus tea) to 1703 microg/kg (green tea). The highest level of BaP was found in lime tea (74,2 microg/kg).

Concentration and particle size distribution of polycyclic aromatic hydrocarbons formed by thermal cooking.

PubMed

Saito, E; Tanaka, N; Miyazaki, A; Tsuzaki, M

2014-06-15

The concentration and particle size distribution of 19 major polycyclic aromatic hydrocarbons (PAHs) emitted by thermal cooking were investigated. Corn, trout, beef, prawns, and pork were selected for grilling. The PAHs in the oil mist emitted when the food was grilled were collected according to particle size range and analysed by GC/MS. Much higher concentrations of PAHs were detected in the oil mist emitted by grilled pork, trout, and beef samples, which were rich in fat. The main components of the cooking exhaust were 3- and 4-ring PAHs, regardless of food type. The particle size distribution showed that almost all the PAHs were concentrated in particles with diameters of <0.43 μm. For pork, the toxic equivalent of benzo[a]pyrene accounted for 50% of the PAHs in particles with diameters of <0.43 μm. From these results, we estimated that >90% of the PAHs would reach the alveolar region of the lungs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Flow cytometry, morphometry and histopathology as biomarkers of benzo[a]pyrene exposure in brown bullheads (ameiurus nebulosus)

USGS Publications Warehouse

Grady, Andrew W.; McLaughlin, Ronald M.; Caldwell, Charles W.; Schmitt, Christopher J.; Stalling, David L.

1992-01-01

Brown bullheads were given a single intraperitoneal dose of 0, 5, 25 or 125 mg kg−1 benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon, and evaluated over 18 months. Flow cytometric analyses of hepatocyte DNA content indicated an increase in DNA synthesis in BaP-exposed fish prior to day 14 post-exposure. Thereafter, all flow cytometric variables returned to initial levels. Histopathological evaluation of livers from fish sampled at 18 months revealed significant differences among treatments in the amount of hepatic macrophage ceroid pigmentation and basophilic staining intensity. No neoplasms or changes in blood cell DNA content were detected. Significant morphometric variations existed among fish, but differences between sexes overshadowed differences attributable to dose. Flow cytometry yielded no evidence of long-term DNA alterations from a single exposure to BaP; however, the differences detected by DNA analysis shortly after the toxic event suggest that flow cytometric cell cycle analysis may be useful for documenting continuing exposures.