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PubMed2003

Benzo[a]pyrene enhances lipid peroxidation induced DNA damage in aorta of apolipoprotein E knockout mice.

The genotoxic compound benzo[a]pyrene (B[a]P) enhances atherosclerotic plaque progression, possibly by inducing oxidative stress and subsequent lipid peroxidation (LPO). Since LPO plays a key role in atherosclerosis, stable LPO derived DNA modifications such as 1,N6-ethenodeoxy-adenosine (epsilondA) and 3,N4-ethenodeoxy-cytidine (epsilondC) may be useful biomarkers for in vivo oxidative stress. In this study, benzo[a]pyrene-diol-epoxide (BPDE)-DNA, epsilondA and epsilondC were determined by 32P-postlabelling in apolipoprotein E knockout (ApoE-KO) mice treated with 5mg/kg B[a]P by gavage. After 4 days, BPDE-DNA adduct levels were higher in aorta (10.8 +/- 1.4 adducts/10(8) nucleotides) than in lung (3.3 +/- 0.7, P < 0.05), which is a known target organ for B[a]P. Levels of epsilondA were higher in aorta of B[a]P-exposed animals than in unexposed controls (8.1 +/- 4.4 vs 3.4 +/- 2.1 adducts per 10(8) parent nucleotides, P < 0.05). On the other hand, epsilondC levels were not affected by B[a]P exposure. Serum low density lipoprotein (LDL) levels were lower in B[a]P-exposed mice than in controls (9.3 +/- 3.7 and 13.3 +/- 4.0mmol/l, respectively), whereas high density lipoprotein (HDL) levels were higher (1.4 +/- 1.6 and 0.4 +/- 0.3mmol/l, respectively). Consequently, a three-fold difference in the LDL/HDL ratio was observed (P = 0.001). epsilondA levels were positively related with plasma HDL concentrations (R = 0.68, P = 0.02), suggesting that the HDL mediated protection of the vessel wall against reactive lipid peroxides was reduced in B[a]P-exposed apoE-KO mice. Our observations show that direct as well as lipid peroxidation induced DNA damage is formed by B[a]P in aorta of apoE-KO mice, which may be involved in atherosclerotic plaque progression. This study further indicates that etheno-DNA adducts are useful biomarkers for in vivo oxidative stress in atherosclerosis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Effects of catechol on the induction of tumors in mouse skin by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes.

Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and enantiomeric 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes (BaP-7,8-diols) in mouse skin. Similar to enhancement of BaP carcinogenesis, repeated concurrent applications of catechol and (+/-)-BaP-7,8-diol to mouse skin strongly enhanced (+/-)-BaP-7,8-diol tumor multiplicity and tumor incidence, and decreased latency. Co-application of catechol with the racemic or either of the enantiomers of BaP-7,8-diol in a two-stage initiation--promotion protocol increased the tumor initiating activity of racemic BaP-7,8-diol, similar to that of BaP, by approximately 50%, but had no statistically significant effect on the tumor initiating activity of the (+)- or (-)-enantiomers in mouse skin. Thus, catechol is as potent a co-carcinogen with (+/-)-BaP-7,8-diol as it is with BaP. However, as tested here catechol is a weak co-initiator when applied with (+/-)-BaP-7,8-diol or BaP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1990

Inhibition of the binding of 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to DNA in mouse skin epidermis by 1-ethynylpyrene.

The effects of 1-ethynylpyrene (EP), 1-vinylpyrene (VP) and 2-ethynlnaphthalene (EN) on the covalent binding of 7,12-dimethylbenz[a]anthracene (DMBA) and of benzo[a]-pyrene (B[a]P) to the epidermal DNA in mouse skin were investigated. When applied topically, 5 min before an initiating dose of 10 nmol DMBA or of 200 nmol B[a]P, EP was an effective inhibitor of the formation of the covalent complexes of these procarcinogenic polycyclic aromatic hydrocarbons (PAHs) with the epidermal DNA. VP, applied under the same conditions, was a significantly less effective inhibitor of the binding of DMBA to DNA and showed even weaker inhibition of the binding of B[a]P. EN was ineffective as an inhibitor of the binding of either DMBA or B[a]P. These results establish that both the pyrene nucleus and the ethynyl substituent of EP contribute to the effective inhibition of the binding of DMBA and B[a]P to the epidermal DNA of mouse skin. No significant changes in the ratios of the anti- to the syndiol epoxide-DNA adducts of DMBA or of B[a]P were produced by doses of EP that produced inhibitions of the binding to DNA. At doses of VP that inhibited covalent binding of both DMBA and B[a]P, no changes in DMBA-DNA adduct distributions were observed but changes in the relative proportions of several B[a]P-DNA adducts were noted. These data are discussed in terms of the potential of aryl acetylenes to act as suicide inhibitors (mechanism-based inactivators) of cytochrome P450-dependent monooxygenase isozymes.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Formation and persistence of benzo[a]pyrene--DNA adducts in different tissues of C57BL/10 and DBA/2 mice.

Synchronous fluorescence spectrophotometry (SFS) developed to study benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)--DNA adducts was used to measure the formation and disappearance of DNA adducts in the lung, liver, kidney, spleen and small intestine of genetically responsive C57BL/10 (B10) and nonresponsive DBA/2 (D2) mice. After single stomach intubation of 100 mg/kg of benzo[a]pyrene (B[a]P) in both strains, binding of BPDE to DNA reached a peak 48 h after treatment. However, the levels of binding in the lung, liver, kidney and spleen were higher in D2 than in B10 mice. In contrast to this, in the small intestine the higher level of BPDE binding was found in B10 mice and reached its maximum 24 h earlier. Thereafter a very rapid drop in the level of BPDE--DNA adducts to a value of approximately 50% after 48 h was observed in this tissue. In the other tissues of the B10 mice the rate of adducts removal was slower, but by 14 days after treatment 90-100% of adducts were removed. In the D2 mice up to the 4th day after treatment the rates of removal of the BPDE--DNA adducts were similar to that of the B10 mice. Thereafter the level of bound hydrocarbon decreased at a slower rate. During the whole period after B[a]P treatment distinct differences between organs in the amount of BPDE--DNA adducts were observed. In D2 mice the highest level of binding was found in the spleen followed by the lung, kidney, liver and small intestine. In B10 mice the highest level of binding was observed in the DNA of small intestine. The data suggest that the decreased rate of B[a]P metabolism in D2 mice may be at least in some tissues the reason of higher binding of BPDE--DNA adducts in comparison with B10 mice.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Flanking base effects on the structural conformation of the (+)-trans-anti-benzo[a]pyrene diolepoxide adduct to N2-dG in sequence-defined oligonucleotides.

Conformations of the trans adduct of (+)-anti-benzo[a]pyrene -7,8-dihydrodiol-9,10-epoxide (BPDE) to N2-guanine, the major stable DNA adduct of the environmental carcinogen benzo[a]pyrene, were studied as a function of flanking bases in single-stranded and in double-stranded oligonucleotides. Three 11mer oligonucleotides d(CTAT-G1G2G3TATC) were synthesized containing the (+)-trans-anti-BPDE adduct at one specific guanine of the GGG sequence (a known mutational hot spot). Polyacrylamide gel electrophoresis of the three single-stranded oligonucleotides showed that the adduct bound to G2 or G3 (5'-flanking base guanine) caused significantly stronger retardation than the same adduct bound to G1 (5'-flanking base thymine). The strength of the carcinogen-base interaction was reflected in the spectroscopic properties of the pyrenyl moiety. Low temperature fluorescence measurements under line-narrowing (FLN) or non-line-narrowing (NLN) conditions showed that in single-stranded form the adduct at G2 or G3 (5'-flanking base guanine) adopts a conformation with strong interaction with the bases. This was also observed for the same adduct at the sequence AGA. In contrast, the (+)-trans-anti-BPDE adduct with a 5'-flanking thymine exists in a primarily helix-external conformation. Similar differences were observed in the double-stranded oligonucleotides: the adducts at G2 and G3 were found to exist in similar conformational equilibria, again with significant carcinogen-base interactions, while the adduct at G1 showed a predominantly external conformation. The nature of the 3'-flanking base appeared to have little influence on the conformational equilibrium of the (+)-trans-anti-BPDE-guanine adduct. The results could provide insight into the mutational specificity and flanking base effects observed for (+)-anti-BPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Differential recognition of stereochemically defined base adducts by antibodies against anti-benzo[a]pyrene diol-epoxide-modified DNA.

The configurational isomers of benzo[a]pyrene diol-epoxide exhibit a range of reactivity, adduct profiles, genotoxic, mutagenic and tumorigenic responses. Whilst the (+)-enantiomer of 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) is the most potent genotoxic species, studies dealing with many critical aspects of BPDE genotoxicity have predominantly been done with the racemic mixture of anti-BPDE. By utilizing highly sensitive non-competitive immunoassays, we have shown that both polyclonal and monoclonal antibodies developed against anti-BPDE-modified DNA exhibit a high degree of stereospecific adduct selectivity with 11mer oligodeoxynucleotides containing a single well-defined base adduct. The polyclonal antibody (PAb BP1) distinctly recognized the highly carcinogenic lesion (+)-anti-BPDE-N2-dG with a 40-fold preference over the (-)-anti-BPDE-N2-dG adduct. In contrast, the monoclonal antibody (MAb 5D2) bound avidly to (-)-anti-BPDE-N2-dG and exhibited very little affinity for the (+)-anti-BPDE-N2-dG adduct. The overall sensitivity of detection of polyclonal antibodies for adducts in (+/-)-anti-BPDE-modified DNA was about 90-fold higher than monoclonal antibodies. Neither antibody showed any detectable reactivity with (+)-or (-)-anti-BPDE-N6-dA and with unmodified DNA antigens. The distinct preference of antibodies for particular enantiomeric adducts was observed in both single and duplexed oligomeric conformations. The demonstrated differential interaction of antibodies with the established conformations of (+)- and (-)-enantiomer anti-BPDE-DNA adducts (de los Santos et al., Biochemistry, 31, 5245-5252, 1992), has significant implications for in vitro and in vivo adduct processing and risk assessment biomonitoring studies.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts and increased p53 protein in mouse skin.

p53 protein expression has been shown to increase in response to DNA damage in cell culture systems. We have studied p53 expression and benzo[a]pyrene (B[a]P)-induced DNA-damage in the form of benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts as measured by synchronous fluorescence spectrophotometry (SFS) in B[a]P-treated C57BL/6 mouse skin. Polyclonal murine antibody CM5, which is comparable to human CM1, detecting both wild-type and mutated protein, was used. BPDE-DNA adducts reached their maximum at 24 h after all dosage regimens, but were very well detectable also at 12 and 48 h after the treatment, while no adducts were measurable at 1 week and thereafter. p53 expression was seen in 9/17 (53%) skin samples from mouse treated with 500 microgram of B[a]P 12-48 h after the treatment, while all 25 (100%) cases of similarly treated mouse skins were negative after 30 weeks of the treatment. Only one positive sample of total 11 was found among mice treated with repeated 62.5 micrograms doses and this was 24 h after the last treatment. After one 62.5 micrograms dose all mice were negative. This is the first report of an association of p53 protein with DNA damage in vivo and gives support for the putative function of p53 in cellular defense machinery towards chemical damage.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1994

Separation and characterization of post-labeled DNA adducts of stereoisomers of benzo[a]pyrene-7,8-diol-9,10-epoxide by immobilized boronate chromatography and HPLC analysis.

The carcinogenic polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) is enzymatically activated in cells to an ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10- epoxide (BaPDE), which reacts with DNA to form covalent adducts involved in the initiation of cancer. Previously, a post-labeling procedure that uses adenosine-5'-O-(3'-[35S]-thiotriphosphate) was developed to facilitate adduct analysis by HPLC. The much greater carcinogenic potency of (+)-anti-BaPDE makes it essential to be able to separate and identify the adducts formed by all four BaPDE enantiomers in DNA of cells exposed to BaP. Reversed-phase HPLC (RPHPLC) resolved the major (+)-anti-BaPDE-N2-deoxyguanosine [(+)-anti-BaPDE-N2-dG] adduct from the (+)-syn-BaPDE-N2-dG adduct. However, anti-BaPDE-N2-dG adducts formed by (+)- and (-)-anti-BaPDE were not resolved. By using ion-pair RPHPLC (IP-RPHPLC) with tetrabutylammonium phosphate, the [35S]post-labeled (-)-anti-BaPDE-N2-dG adduct eluted 3 min prior to the [35S]labeled (+)-anti-BaPDE-N2-dG adduct. In contrast, the major syn-BaPDE-N2-dG adducts were resolved better by RPHPLC than by IP-RPHPLC. The difference in conditions required for optimal separation of anti- and syn-BaPDE-DNA adducts necessitated the development of an immobilized boronate chromatography technique for the separation of anti- from syn-BaPDE-DNA adducts prior to analytical HPLC analysis. At 4 degrees C and with elution buffers containing high salt concentrations, the [35S]post-labeled anti-BaPDE-DNA adducts were selectively retained by a boronate column whereas the [35S]labeled syn-BaPDE-DNA adducts were not. Analysis of the multiple BaP-DNA adducts formed in BaP-treated hamster embryo cells by these techniques gave results comparable to those obtained by other methods. The major BaP-DNA adducts were anti-BaPDE-N2-dG, 14% from (-)- and 86% from (+)-anti-BaPDE. The ability of these techniques to detect low levels of PAH-DNA adducts because of the high specific radioactivity of 35S and to separate the DNA adducts formed by stereoisomeric PAH diol epoxides adducts by boronate by stereoisomeric PAH diol epoxides adducts by boronate chromatography and HPLC will facilitate studies of the role of individual PAH-DNA adducts in the induction of biological effects such as toxicity and carcinogenesis.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

p53 protein expression is correlated with benzo[a]pyrene-DNA adducts in carcinoma cell lines.

p53 inhibits cell cycle progression and DNA damaging cytostatics induce p53 protein expression, indicating that p53 responds to DNA damage. We have measured benzo[a]pyrene (BP)-induced DNA damage in association with p53 expression. The most relevant DNA adducts for carcinogenesis, benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts, were measured by synchronous fluorescence spectrophotometry and p53 immunohistochemistry using polyclonal antibody CM1, which detects both wild-type and mutated forms of p53. Activation of BP in A-549 lung carcinoma and MCF-7 breast adenocarcinoma cell lines containing wild-type p53 was followed by an increase in p53 protein expression. alpha-Naphthoflavone, an inhibitor of cytochrome P450 (CYP)1A1, decreased both the formation of diolepoxide metabolites and the p53 response. The cell lines not able to activate BP, A-427 and SK-LU-1 (both human lung carcinomas), SK-MES-1 (human lung squamous carcinoma) and human fibroblasts, did not show any increase in p53 immunohistochemistry. The OVCAR-3 ovarian adenocarcinoma cell line, containing a mutation in exon 7 of p53, and the SK-LU-1 cell line expressed very high levels of p53 protein before BP treatment and no increase in p53 immunohistochemistry was seen. These findings indicate that p53 protein is part of the response of the cells to BP-induced DNA damage.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

TPA decreases the p53 response to benzo[a]pyrene-DNA adducts in vivo in mouse skin.

TPA, a well-known tumor promoter, decreased the response of nuclear p53 immunoreactivity to benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts in C57BL/6 mouse skin in vivo. A dose-dependent increase in both the level of BPDE-DNA adducts and nuclear p53 immunoreactivity was found in mice treated topically with 50-750 microg benzo[a]pyrene. Such a positive correlation between the adducts and p53 positivity was suggested by an earlier study. Since p53 probably functions in DNA damage control, interference by TPA with the p53 response could be a mechanism in TPA-induced tumor promotion. Whether such a mechanism is more general in tumor promotion deserves further study.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1983

The persistence of benzo[a]pyrene diol-epoxide deoxyguanosine adduct in mouse skin and its disappearance in rat skin.

Male Swiss mice and Wistar rats, susceptible and resistant, respectively, to the carcinogenic effects of benzo[a]pyrene, were treated topically with 250 nmol/mouse and 1000 nmol/rat of tritium labelled benzo[a]pyrene (BaP). The initial formation of BaP diol-epoxide deoxyguanosine adduct was approximately similar in the skin epidermis of the two species. After 3 weeks, the persistence of some 6.5% of initial BaP diol-epoxide deoxyguanosine was observed in mouse skin DNA, while this adduct was completely removed from DNA of rat skin. The total excision of BaP diol-epoxide deoxy-guanosine adduct in rat epidermis may contribute in part for the relative resistance of rat skin to the carcinogenic actions of BaP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1986

Preferential binding of the carcinogen benzo[a]pyrene to DNA in active chromatin and the nuclear matrix.

Rat liver nuclei or hepatocytes were incubated with the proximate carcinogen, benzo[a]pyrene (BP) and its ultimate carcinogen, anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE). Following carcinogen exposure, nuclei were fractionated by micrococcal nuclease digestion and stepwise extraction to yield an active chromatin fraction enriched in transcribed versus non-transcribed genes, a bulk chromatin fraction, a high-salt-extracted chromatin fraction and a nuclear matrix fraction containing elevated concentrations of transcribed and nontranscribed genes. BP binds more readily to DNA of active chromatin and nuclear matrix than to bulk chromatin. Since low concentrations of BPDE also selectively damage active chromatin and matrix DNA, selectivity is not due to the subnuclear location of enzymes which activate BP to BPDE. Higher BPDE concentrations cause more uniform DNA damage. Selective carcinogen attack may result from an accessible DNA conformation in active chromatin and matrix or from partitioning of carcinogen in the nuclear membrane.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1993

DNA repair in congenic mice: possible influence of a chromosome 4 genetic region on the rate of benzo[a]pyrene-induced DNA adduct removal.

An attempt was made to assign mouse lifespan-associated interstrain differences in DNA repair to a specific chromosomal region using a set of congenic mice. The sensitive 32P-postlabeling assay was employed to measure the removal of benzo[a]pyrene-induced DNA adducts in liver DNA of three different chromosome 4 congenic mouse strains: B6.C-H-15c, B6.C-H-16c, and B6.C-H-26c and the two parental strains, C57B1/6 and BALB/c. The removal of the one main adduct detected, trans-(7R)-N2-[10-(7 beta,8 alpha,9 alpha-trihydroxy)-7,8,9,10- tetrahydrobenzo(a)-pyrene]-yl-deoxyguanosine (BPDE-N2-dG), in liver DNA of C57Bl/6 and BALB/c mice between one and three days after treatment, was approximately 86% and 57%, respectively. The percentage removal of BPDE-N2-dG in two of the three congenic mouse strains, B6.C-H-16c and B6.C-H-26c, resembled that found in BALB/c, whereas the third strain, B6.C-H-15c, removed about the same amount as C57B1/6, i.e., approximately 88% of BPDE-N2-dG between one and three days after treatment. The usefulness of congenic mouse strains for identifying genes putatively involved in aging and/or disease susceptibility is discussed.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2006

Phytochemicals induce breast cancer resistance protein in Caco-2 cells and enhance the transport of benzo[a]pyrene-3-sulfate.

We have previously reported that breast cancer resistance protein (BCRP) is involved in the transport of phase II metabolites of the food carcinogen benzo[a]pyrene (BP) in the human intestinal cell line Caco-2. Furthermore, the expression of BCRP seemed most likely to be aryl hydrocarbon receptor (AhR) dependent. Since numerous plant-derived anticarcinogens with AhR-agonistic activity have been identified to date, in the present study we investigated the effects of naturally occurring dietary compounds and tert-butyl hydroquinone (TBHQ) for their effects on BCRP expression. In Caco-2 cells, the most pronounced induction of BCRP expression could be observed after treatment with TBHQ (100 microM), dibenzoylmethane (DBM, 50 microM), and quercetin (25 microM), while green tea component (-)-epicatechin (50 microM) decreased BCRP expression. On mRNA level, quercetin, chrysin, flavone, and indole-3-carbinol showed a strong inducing effect, while genistein had no effect on BCRP mRNA expression. Curcumin and resveratrol showed a strong effect on BCRP induction in MCF-7 wild-type cells but no response in AhR-deficient MCF-7AHR(200) cells, supporting our hypothesis that BCRP is regulated via AhR-dependent signaling pathways. Inhibition of proteasome-mediated degradation of ligand-activated AhR caused a "superinduction" of BCRP mRNA. Antioxidant responsive element activators sulforaphane and diethylmaleate (DEM) had no inducing effect on BCRP mRNA expression. Caco-2 cells pretreated with quercetin or DBM showed an enhancement of apically transported benzo[a]pyrene-3-sulfate, indicating that induced BCRP was functionally active. In conclusion, apart from the modulation of detoxifying enzymes in the intestine, induction of BCRP by dietary constituents may contribute to the detoxification of food-derived procarcinogens such as BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1993

Fluorescence line-narrowing studies of antibody-benzo[a]pyrene tetrol complexes.

Benzo[a]pyrene tetrol (BPT) was used as a fluorescent probe to investigate the nature of antigen binding by two different monoclonal antibodies (MAb) that recognize a variety of derivatives of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrenes (BPDE). Fluorescence line-narrowed spectra of the physical complexes of BPT formed with antibodies 8E11 and 3C3 were recorded at 4 K by employing vibronic excitation into the S1 electronic state. The frequencies of the vibrational modes of the S1 state were only marginally affected, though changes in relative intensities of some bands were observed. Fluorescence spectra recorded at 77 K by excitation into the S2 state showed that the (0,0) fluorescence emission of BPT was shifted to red on complex formation. Intensity ratios of the (0,0) band and the main vibrational band at 1300 cm-1 were used to assess the degree of interior binding of the chromophore. Quenching studies with acrylamide were employed to designate the complexes as type I, solvent inaccessible, or type II, solvent accessible. These studies also indicated that antibody 3C3 complexes tend to be more heterogeneous compared to the 8E11 complex. Deuterated BPT-d-12 also formed complexes with both antibodies, however, with different quenching behavior.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2006

Analysis of benzo[a]pyrene deactivation mechanisms in rats.

The experimental data on the effects of a widespread carcinogen, benzo[a]pyrene (BP), on individual reactions of rats were treated using mathematical-statistical methods. The individual reactions were analyzed in dependence of doses and modes of administration (single or chronic). The analysis revealed a statistically significant correlation between life span and urinary content of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-BP) in rats treated with BP. The calculated regression equations revealed that the individual sensitivity to carcinogen in case of the BP single administration to rats is mainly determined by efficiency of excretion of the BP active forms out of the organism, whereas after chronic BP administration it is determined by mechanisms of enzymatic deactivation of BP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1991

[A mutant strain of Drosophila simulans sensitive to the toxic and mutagenic action of benz(a)pyrene].

A 364 yv strain sensitive to the toxic effect of benzo(a)pyrene (BP) was identified among 49 mutant strains of Drosophila simulans. Heterozygotes female 364 x male Turku obtained by crossing 364 yv species with those of wild BP-resistant Turku strain were more sensitive than female Turku x male 364 heterozygotes to both toxic and mutagenic effects of the carcinogen in the test of induction of somatic mosaicism with the yellow marker. Non-carcinogenic pyrene appeared weekly toxic and non-mutagenic. Possible mechanisms of 364 yv strain sensitivity to BP as well as vistas in application of the strain for monitoring genotoxic environmental pollution are discussed.

Animals↗
PubMed1985

Detection of benzo(a)pyrene:DNA adducts in human white blood cells.

Metabolic activation of benzo(a)pyrene (BP) to its ultimate carcinogenic form, 7 beta, 8 alpha-diol-9 alpha, 10 alpha-benzo(a)pyrene epoxide (BPDE), and the binding of BPDE to DNA are important steps in BP carcinogenicity in experimental animals. Since people of certain occupations are exposed to high concentrations of BP, we have used enzyme-linked immunosorbent assay and ultrasensitive enzymatic radioimmunoassay to measure BPDE:DNA adducts in white blood cells from 2 of these occupational groups. Seven of 28 samples from roofers and 7 of 20 samples from foundry workers were positive for BPDE:DNA adducts (range, 2 to 120 fmol BPDE/50 micrograms DNA). In a group of nine volunteers without these industrial exposures to BP, the two positive DNA samples were from cigarette smokers. Control DNA obtained from human lymphocyte cell line RPMI 4265 was negative. These results indicate that the metabolic activation of BP and formation of BPDE:DNA adducts occurs in humans.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗