Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyrenes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,153 records · Page 64Linked to original sources
PubMed1981

Studies on the in vitro transfer of DNA binding benzo[a]pyrene metabolites from rat hepatocytes to human fibroblasts.

The release and reabsorption of benzo[a]pyrene (BP) metabolites were studied in isolated rat hepatocytes incubated with BP. There was a rapid uptake of BP by the hepatocytes which was followed by an excretion of organic as well as water-soluble metabolites. Upon further incubation the BP-dihydrodiols and BP-phenols were reabsorbed by the cells and finally excreted as water-soluble conjugates. The metabolism of BP by the hepatocytes also resulted in the formation and release of reactive intermediates to the incubation medium. The DNA-binding intermediates released from the cells were consistent with trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene-9,10-oxide(s) and 9-hydroxybenzo[1]pyrene-4,5-oxide(s). The BP-metabolites were found to bind to hepatocyte and fibroblast DNA. The degree of DNA binding was estimated as the formation of DNA strand breaks. BP metabolites formed within the hepatocytes and transferred to the fibroblasts were found to induce DNA strand breaks in the latter cells. Addition of DNA to the medium markedly decreased the fraction of single stranded DNA in these cells. Under conditions where the excretion from hepatocytes of BP-phenols and BP-dihydrodiols were increased, the amount of DNA strand breaks in the fibroblasts increased.

Animals↗
PubMed2002

Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring.

A chemiluminescence immunoassay (CIA) utilizing antiserum elicited against DNA modified with (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]- pyrene (BPDE) has been developed and validated to study the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human tissues. Advantages include a low limit of detection for 10b-(deoxyguanosin-N(2)-yl)-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG, approximately 1.5 adducts/10(9) nucleotides using 20 micro g DNA) and a high signal-to-noise ratio (> or =100). The CIA BPDE-DNA standard curve gave 50% inhibition at 0.60 +/- 0.08 fmol BPdG (mean +/- SE, n = 30), which was a 10-fold increase in sensitivity compared with the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). Calf thymus DNA modified with [1,3-(3)H]BPDE was assayed by radiolabeling, (32)P-postlabeling, DELFIA and CIA, and all assays gave similar values. Liver DNAs from mice exposed to 0.5 and 1.0 mg [7,8-(3)H]benzo[a]pyrene (BP) were assayed by the same four assays and a dose-response was obtained with all assays. The BPDE-DNA CIA was further validated in MCL-5 cells exposed to 4 micro M BP for 24 h, where nuclear and mitochondrial DNA adduct levels were associated with an increase in DNA tail length measured by the Comet assay. Human peripheral blood cell (buffy coat) DNA samples (n = 43) obtained from 25 individuals who were either colorectal adenocarcinoma patients or controls were assayed by BPDE-DNA CIA. Three samples (7%) were non-detectable, and the remaining 40 samples had values between 0.71 and 2.21 PAH-DNA adducts/10(8) nucleotides. The intra-assay coefficient of variation (CV), for four wells on the same microtiter plate, was 1.85%. Sufficient DNA for two assays, on separate plates, was available for 38 of the 43 samples, and the PAH-DNA adduct values obtained were highly correlated (r(2) = 0.95). Coded duplicate DNA samples from 15 individuals were assayed four times gave an inter-assay CV of 13.8%.

Adenocarcinoma↗
PubMed1982

Different patterns of benzo[a]pyrene metabolism of purified cytochromes P-450 from methylcholanthrene, beta-naphthoflavone and phenobarbital treated rats.

An improved high-pressure liquid chromatography system was used to analyze the amount of benzo[a]pyrene metabolites formed in reconstituted microsomal mixed-function oxidase systems containing different cytochromes P-450. We separated twelve identified and seven unknown metabolites of BP which included three diols: the 9,10-, 4,5-and 7,8-dihydrodiols; four phenols, 9-,7-, 1-, and 3-hydroxybenzo[a]pyrene (OH-BP); and three quinones: the 1,6-. 3,6-, and 6,12-quinones. Two additional peaks co-migrated with synthetic 4-OH-BP and 5-OH-BP, respectively. The former, designated fraction 1, was shown by u.v. spectra to contain primarily the 4,5-epoxide with small amounts of 4-OH-BP. The total metabolism of BP was found to be approximately 20-fold greater with the cytochrome P-450 from the 3-methylcholanthrene (P-450 3-MC) and beta-naphthoflavone (P-450 BNF) treated rats than with the phenobarbital preinduced cytochrome P-450 (P-450 BP). 3-OH-BP ad 9-OH-BP were the major phenolic products for both P-450 3-MC and P-450 BNF whereas the 3-OH-BP and 1-OH-BP were the major phenolic products for P-450 BP. The ratio of total phenols to diols was found to be 3.34, 4.85 and 0.70 for P-450 3-MC, P-450 BNF and P-450 PB. The major dihydrodiol generated by P-450 3-MC and P-450 BNF was 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, whereas the 9,10-diol was the major diol from P-450 PB. The amount of 1,6- and 3,6-quinones produced was greater than the 6,12-quinone with the P-450 3-MC and P-450 BNF but all three quinones were produced in low and equal amounts by the P-450 PB. In respect to the percent metabolites formed at a given region of the BP, P-450 3-MC and P-450 BNF preferred oxidation at the 1, 3 positions, 6 position and the 7, 8 positions, whereas the P-450 PB preferred oxidation at the 4, 5 position. This study demonstrates the unique positional specificity of different forms of cytochrome P-450 which may regulate the balance between activation and detoxification pathways of polycyclic aromatic hydrocarbon metabolism.

Animals↗
PubMed1982

Benzo[a]pyrene metabolites: formation in rat liver cell-culture lines, binding to macromolecules, and mutagenesis in V79 hamster cells.

Benzo(a]pyrene was metabolized in liver cell lines derived from BC-IV and BD-IV rats which included several chemically-transformed lines (IAR-6-1; IAR-19; IAR-28), one spontaneous transformant (IAR-27) as well as one non-malignant line (IAR-20). Cultures were treated with tritiated benzo[a]pyrene over a 5-day period. The cells and medium were extracted with ethyl acetate and the distribution between organic-soluble and water-soluble metabolites determined. Organic-soluble metabolites consisting of dihydrodiols, phenols and quinones were determined by high-pressure liquid chromatography, and macromolecular binding of BP to each cell line was measured over a 24-h period. Comparisons between binding and overall metabolism were not directly proportional in these liver cell lines. However, there was a positive correlation for benzo[a]pyrene mutagenesis in the V-79 hamster cell assay with 8-azaguanine as a marker when the cell lines with the highest (IAR-20) and lowest (IAR-27) metabolic competence were used as activating cell layers.

Animals↗
PubMed1983

Specificity of rat liver cytochrome P-450 isozymes in the mutagenic activation of benzo[a]pyrene, aromatic amines and aflatoxin B1.

The ability of three purified forms of rat liver cytochrome P-450 to metabolically activate benzo[a]pyrene, trans-benzo-[a]pyrene-7,8-dihydrodiol, 2-aminofluorene, aflatoxin B1, dimethylnitrosamine, and a pyrolysis product of tryptophan(3-amino-1-methyl-5H-pyrido(4,3-b)indole) (Trp-P-2) to mutagenic products was examined using Salmonella typhimurium strains TA98 and G46 in a reconstituted monooxygenase system. The isozymes examined were cytochrome P-450-PB (the major phenobarbital inducible form), and the two major 3-MC inducible forms (cytochromes P-448(52) and P-448(55)). Cytochromes P-448(52) and P-448(55) preferentially metabolize 2-aminofluorene and Trp-P-2 to mutagenic products. However, only cytochrome P-448(55) metabolizes benzo[a]pyrene and its 7,8-dihydrodiol derivative to mutagenic products. Both cytochrome P-448(52) and P-448(55) metabolize aflatoxin B1 to mutagenic products at a much faster rate than cytochrome P-450-PB. Dimethylnitrosamine was not activated by any of the isozymes tested.

Aflatoxin B1↗
PubMed1984

Monoclonal antibodies to DNA modified by a benzo[a]pyrene diol epoxide.

Monoclonal antibodies were obtained after fusion of mouse P3 X 63 Ag8.653 myeloma cells with spleen cells isolated from BALB/cCr mice 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. One monoclonal hybridoma line from each type of immunization was grown as ascites tumors or in defined media and characterized in an enzyme linked immunosorbent assay (ELISA). The antibody produced from the spleen cells of a BPDE-I-DNA immunized mouse, designated 5D11, recognizes BPDE-I-DNA and DNA modified by 7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE II) but not unmodified DNA, N-2-acetylaminofluorene (AAF) or 1-nitropyrene (NP) modified DNA, BPDE-II-dG or BPDE-I tetraol. It does recognize BPDE-I-dG but with a much lower affinity than when the adduct is present in DNA. In contrast, antibody 8E11 produced from the spleen cells of a BPDE-I-G-BSA immunized mouse recognizes the monoadduct BPDE-I-dG better than BPDE-I-DNA. It also recognizes BPDE-I tetraol but not BPDE-II-DNA, unmodified DNA, AAF- or NP-DNA or BPDE-II-dG. In a noncompetitive ELISA as little as 3 fmol of BPDE-I-DNA adduct can be detected with either antibody 5D11 or 8E11. The combination of the highly sensitive ELISA and highly specific monoclonal antibodies should be valuable in the detection and quantitation of human exposure to benzo[a]pyrene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene.

Syrian golden hamsters were given intratracheal instillations of glass fibres with or without benzo[a]pyrene suspended in saline, once a fortnight for 52 weeks. The experiment was terminated at week 85. 'Silicotic granulomas' consisting of tightly packed, iron-positive macrophages filled with glass fibres and surrounded by a layer of alveolar epithelial cells were the predominant pulmonary lesion. No mesotheliomas or other tumours of the respiratory tract were observed in hamsters treated with glass fibres alone. There was no indication that glass fibres enhanced the development of respiratory tract tumours induced by benzo[a]pyrene. In hamsters similarly exposed to crocidolite fibres with or without benzo[a]pyrene no mesotheliomas or other respiratory tract tumours were observed either. An explanation for the absence of pulmonary tumours might be that repeated administration of fibres over a period of 52 weeks entails an acute pulmonary reaction after each administration with the implication that the fibres cannot settle down well enough to be able to induce tumours. Another possible explanation is the relatively short duration of the experimental period.

Animals↗
PubMed1987

Spectroscopic studies on double-stranded poly d[(G-C)(G-C)] in B and Z form after covalent modification with the anti diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Poly d[(G-C)(G-C)] in B or Z conformation has been incubated with the anti-diastereomer of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE). Enzymatic hydrolysis, circular dichroism (CD) and light absorption were used to study the binding specificity of anti-BPDE to the right- and left-handed forms of poly d[(G-C)(G-C)]. The effect of anti-BPDE binding on the conformational transition, induced by MnCl2 or NaCl, was also studied. The results obtained demonstrate that in Mn2+-containing solutions, when the ionic conditions are identical, there is only a minor difference in the extent of covalent binding of anti-BPDE to the polynucleotide in right- or left-handed form. A high degree of enantioselectivity of poly d[(G-C)(G-C)] towards (+)-anti-BPDE was observed with both conformational states, although the B form seems to be slightly more selective. With either form, the major adduct in the h.p.l.c. analysis is consistent with trans-N2-10-[(7 beta,8 alpha,9 alpha-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene)-yl]-deoxyguanosine [(+)-anti-BPDE-N2-dG] adducts. A 3 nm bathochromic shift of the light absorption of the pyrene chromophore was observed for the Mn2+-induced left-handed form of the polynucleotide. A similar shift was observed with the NaCl-induced transition only at intermediate NaCl concentrations, where the CD spectra showed a mixture of right- and left-handed forms. The bathochromic shift may be a consequence of a reduced exposure of the chromophore to the aqueous solvent. In poly d[(G-C)(G-C)] modified with anti-BPDE, higher ionic strengths are required to reach optimal B-Z transition compared to unmodified samples. This indicates that there is a restriction in the transition process at the sites of modification. The results have been discussed in terms of two distinct domains in the modified polynucleotide: one 'normal' domain, where an initially rapid transition takes place, and another 'BPDE-domain' involving the modification site and a few adjacent base pairs. It is likely that this domain is associated with the inhibitory effect on the B-Z transition.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1988

Metabolic activation of cyclopenteno[c,d]pyrene by peroxyl radicals.

The conversion of cyclopento[c,d]pyrene (CPP) to forms which are mutagenic to Salmonella typhimurium strain TA98 has been demonstrated in systems which generate peroxyl radicals. The systems examined included prostaglandin H synthase (PHS) and arachidonic acid, 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) and hematin, and the autoxidation of the sulfite ion. In all cases concentration-dependent activation of CPP was observed at hydrocarbon concentrations between 10 and 100 microM. Neither CPP nor the peroxyl radical systems alone were mutagenic or toxic to the tester strain. The use of hydroxygen peroxide with PHS, a peroxidative system which does not yield peroxyl radicals, does not activate CPP. The involvement of a CPP epoxide was examined using 1,1,1-trichloropropene-2,3-oxide. Addition of this epoxide hydrolase inhibitor to incubations of CPP with the PHS/arachidonic acid system resulted in a 210% increase in induced revertants relative to the system in the absence of the inhibitor. The addition of pure rat liver microsomal epoxide hydrolase to incubations of CPP with the 15-HPETE/hematin system resulted in a concentration-dependent loss of mutagenicity, further supporting the intermediacy of an epoxide. The site of metabolism of CPP is the cyclopenteno double bond based on the formation of products which display distinct pyrene-type fluorescence spectra. The involvement of the cyclopenteno double bond also is shown by the inability of the 15-HPETE/hematin system to activate 3,4-dihydrocyclopenteno[c,d]pyrene as a mutagen. CPP is the first environmentally-relevant carcinogenic hydrocarbon found to be activated directly by peroxyl radical systems without prior biotransformation to a diol derivative by the cytochrome P-450 system. These findings expand the range of potentially toxic substrates to be considered for activation by peroxyl radical pathways.

Animals↗
PubMedDate not supplied

Trace analysis of 3-hydroxy benzo[a]pyrene in urine for the biomonitoring of human exposure to polycyclic aromatic hydrocarbons.

Determination of benzo[a]pyrene (BaP) metabolites in urine can provide direct insight into recent exposure to BaP integrated from all uptake routes. In order to detect 3-OH BaP in human urine after exposure to BaP at the workplace, extremely sensitive methods need to be developed. In this paper, a new extraction method is presented, and two laser-based fluorescence techniques are evaluated. Using HPLC with laser-induced fluorescence detection, a detection limit of 8 ng/L was obtained. With laser-excited Shpol'skii spectrometry after chemical derivatization, 3-OH BaP could be detected at even a 0.5-ng/L concentration. In a pilot study, urine samples from coke-oven workers and from occupationally nonexposed control persons were analyzed. In the control samples, the average 3-OH BaP concentration was 8.3 ng/L; the 3-OH BaP concentrations were found to be highly correlated (r2 = 0.89) with urinary 1-OH pyrene, a widely used biomarker for polycyclic aromatic hydrocarbon (PAH) exposure. Significantly elevated 1-OH pyrene concentrations were measured in urine samples from coke-oven workers, but in most samples a corresponding increase of 3-OH BaP was not observed. Possible explanations for this discrepancy are discussed.

Benzopyrenes↗
PubMedDate not supplied

Determination of benzo[a]pyrene and other polycyclic aromatic hydrocarbons (PAHs) at trace levels in human tissues.

A sensitive and rugged gas chromatographic-mass spectrometric (GC-MS) method was developed for determining 11 polycyclic aromatic hydrocarbons (PAHs) in 4-g specimens of human lung, breast, and liver tissue. The method quantitation limit (MQL) was 0.01-0.02 ng/g for benzo[a]pyrene (BaP) and six other five- and six-ring PAHs. The MQL was higher for four-ring PAHs because of their presence at trace levels in method blanks. The average MQLs for pyrene and chrysene were 0.05 and 0.03 ng/g, respectively. The method was applied to 200 human tissue specimens (89 lung, 68 breast, and 43 liver) obtained from patients during surgery. Quality-control results demonstrated average recoveries of 80% or better from reagent controls spiked at the 0.2-ng level and average recoveries from tissue fortified at the 0.25-ng/g level of 66-95%. The precision of the method was determined from duplicate analyses of specimens (16-38% RSD) and from duplicate GC-MS analysis of tissue extracts (8-17%RSD). Benzo[a]pyrene was detected at measurable levels in 87% of the lung specimens. This method makes possible the measurement of ambient levels of PAHs in small samples of human tissue such as those obtained by biopsy.

Benzo(a)pyrene↗
PubMed1983

Binding of pyrene to DNA, base sequence specificity and its implication.

Solubilization as well as spectral studies of pyrene in natural DNA and synthetic deoxypolynucleotide solutions at neutral pH reveal at least two binding modes. Sites I are predominant in native DNA and in poly(dA-dT): poly(dA-dT) whereas sites II are found with denatured DNA and other polynucleotides such as poly(dA):poly(dT) and three different types of guanine containing copolymers which solubilize pyrene to a lesser extent. Spectral comparison with the covalent adducts of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10- tetrahydro-benzo(a)pyrene (anti-BPDE) and the physical complexes of its tetraols lead to the suggestion of a base sequence specific binding model for this carcinogenic metabolite to account for the puzzling fact that although its physical binding is predominantly intercalative, the covalent adducts appear not to be intercalated. It is speculated that in neutral solutions, intercalation may have little, if any, to do with the chemical lesion of this metabolite to the guanine base of the DNA and may, on the contrary, provide an efficient pathway for detoxification.

Chemical Phenomena↗
PubMed2000

Dynamics of the fluorescence properties of pyrene residues appended to oligonucleotide hybridization probes.

The dynamic and static properties of the fluorescence of a pyrene-introduced oligonucleotide 16 mer and its hybrid with a target 32 mer. Their fluorescence quantum yields (< 1%) were much weaker than that of unsubstituted pyrene and their fluorescence lifetime of the major decay components were less than 1 ns. The rapid fluorescence quenching was due to the interaction between the fluorophore and bases in the oligonucleotides. The fluorescence of pyrene was quenched efficiently by TMP and slightly by AMP. The quenching by CMP and GMP were the intermediate case.

Adenosine Monophosphate↗
PubMed2004

Tumor profile of novel p53 heterozygous Tg.AC (v-Ha-ras) bitransgenic mice treated with benzo(a)pyrene and fed dietary N-acetyl-L-cysteine (NAC).

We designed a novel short-term bitransgenic model to better characterize the effects of benzo(a)pyrene (BP) exposure on multi-organ carcinogenesis and to evaluate the effects of a well-recognized antioxidant, N-acetyl-L-cysteine (NAC), on neoplasia. We selected the p53 heterozygous Tg.AC (v-Ha-ras) mouse model for our studies because these mice possess a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele. Both mutations occur frequently in human cancers. In a 2 x 2 experimental design, both female and male mice were fed basal diet alone or containing 3% NAC and administered by gavage corn oil vehicle alone or containing 20 mg BP/kg body weight given twice weekly for 10 weeks. Mice (n = 15 for each grouping and sex) were subsequently observed an additional 18 weeks followed by tissue collection for evaluation of multi-organ pathology. Benzo(a)pyrene increased neoplasia in the thymus, spleen, stomach, and hematopoietic system after 28 weeks. We observed modest NAC-associated decreases in BP-induced pathology of the liver, papilloma formation and hyperplasia in the forestomach, and the occurrence of malignant lymphoma. Benzo(a)pyrene exposure reduced survival to approximately 40% in male mice, suggesting toxicity; however, survival in control groups was approximately 60%. Survival decreased to approximately 30% for females in all groups. We noted a clear, but nonsignificant, 15% decline in body weights of male, but not female, mice fed NAC, although food intake did not differ. Collectively, the data suggested carcinogen and antioxidant-associated effects on neoplasia that appeared sex-dependent. Thus, this novel short-term bitransgenic model may potentially be useful for testing dietary modulation of carcinogenesis.

Acetylcysteine↗
PubMed1995

Fetal mouse susceptibility to transplacental carcinogenesis: differential influence of Ah receptor phenotype on effects of 3-methylcholanthrene, 12-dimethylbenz[a]anthracene, and benzo[a]pyrene.

Genetic backcrosses of C57BL/6 and DBA/2 mice were used to examine the influence of maternal and fetal polymorphisms at the Ahr locus on susceptibility to transplacental carcinogenesis by 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene, and benzo[a]pyrene. (C57BL/6 x DBA/2) F1 mothers were backcrossed to DBA/2 males, and DBA/2 females to F1 males to produce both Ahr-responsive (Ah+) and nonresponsive (Ah-) fetuses carried by mothers that were themselves either Ah+ or Ah-. 3-Methylcholanthrene was given intragastrically on gestation days 13-18 and 7,12-dimethylbenz[a]anthracene or benzo[a]pyrene on day 17 as a single intraperitoneal dose. Ahr phenotype was determined by the zoxazolamine sleeping time test after beta-naphthoflavone pretreatment at 6 weeks of age. The offspring were examined for tumours at 1 year. Both 3-methylcholanthrene and 7,12-dimethylbenz[a]anthracene treatments resulted in a two- to five-fold greater incidence and multiplicity of lung and liver tumours in the Ah+ offspring compared with that in Ah- littermates. By contrast, there was no difference between Ah+ and Ah- offspring with regard to numbers of tumours caused by benzo[a]pyrene. Maternal Ahr phenotype appeared to play a role also, in that the offspring of the Ahr-responsive F1 mothers developed fewer tumours per unit dose than those of the nonresponsive DBA/2 mothers. The effect of maternal phenotype on risk was three- to five-fold. Fetal and maternal phenotype combined yielded a 10- to 20-fold risk differential for transplacental carcinogenesis by the methylated compounds, with greatest risk experienced by responsive fetuses in nonresponsive mothers, and least by nonresponsive progeny of responsive mothers.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

Mutagenic activation of biliary metabolites of benzo(a)pyrene by beta-glucuronidase-positive bacteria in human faeces.

Human faeces hydrolysed synthetic beta-D-glucuronides of both p-nitrophenol and phenolphthalein. The origin of this activity in faeces was localised in the bacterial pellet fraction after centrifugation. Ninety-seven bacterial strains with beta-glucuronidase activity isolated from fresh human faeces were identified as species of Bacteroides, Peptostreptococcus, Fusobacterium, Propionibacterium, Clostridium, Eubacterium and Bifidobacterium. They were classified into two groups according to their activity against two synthetic beta-D-glucuronides. One group hydrolysed p-nitrophenyl glucuronide and phenolphthalein glucuronide to the same extent and the other hydrolysed p-nitrophenyl glucuronide much more strongly than phenolphthalein glucuronide. The bile of rats given benzo(a)pyrene by mouth was tested for mutagenicity in the presence and absence of cell-free extracts of human faeces and bacteria. Extracts of beta-glucuronidase-positive bacteria increased the mutagenicity of metabolites of benzo(a)pyrene, as did faecal extracts, but extracts of beta-glucuronidase-negative bacteria did not. D-Saccharic acid-1,4-lactone inhibited the increase in mutagenicity produced by the faecal extracts and extracts of beta-glucuronidase-positive bacteria except for Peptostreptococcus strains 204 and 952. These results indicate that some intestinal bacteria have beta-glucuronidases heterogenous in substrate specificity and that they may be involved in mutagenicity of benzo(a)pyrene in the intestinal tract.

Adult↗
PubMed2000

Cancer risk estimation for mixtures of coal tars and benzo(a)pyrene.

Two-year chronic bioassays were conducted by using B6C3F1 female mice fed several concentrations of two different mixtures of coal tars from manufactured gas waste sites or benzo(a)pyrene (BaP). The purpose of the study was to obtain estimates of cancer potency of coal tar mixtures, by using conventional regulatory methods, for use in manufactured gas waste site remediation. A secondary purpose was to investigate the validity of using the concentration of a single potent carcinogen, in this case benzo(a)pyrene, to estimate the relative risk for a coal tar mixture. The study has shown that BaP dominates the cancer risk when its concentration is greater than 6,300 ppm in the coal tar mixture. In this case the most sensitive tissue site is the forestomach. Using low-dose linear extrapolation, the lifetime cancer risk for humans is estimated to be: Risk < 1.03 x 10(-4) (ppm coal tar in total diet) + 240 x 10(-4) (ppm BaP in total diet), based on forestomach tumors. If the BaP concentration in the coal tar mixture is less than 6,300 ppm, the more likely case, then lung tumors provide the largest estimated upper limit of risk, Risk < 2.55 x 10(-4) (ppm coal tar in total diet), with no contribution of BaP to lung tumors. The upper limit of the cancer potency (slope factor) for lifetime oral exposure to benzo(a)pyrene is 1.2 x 10(-3) per microgram per kg body weight per day from this Good Laboratory Practice (GLP) study compared with the current value of 7.3 x 10(-3) per microgram per kg body weight per day listed in the U.S. EPA Integrated Risk Information System.

Animals↗
PubMed2006

Chemotherapeutic efficacy of paclitaxel in combination with Withania somnifera on benzo(a)pyrene-induced experimental lung cancer.

Lung cancer is one of the leading causes of cancer death in the world and is notoriously difficult to treat effectively. In the present study, male Swiss albino mice were divided into five groups of six animals each: group I animals received corn oil orally and served as a control; group II cancer-induced animals received benzo(a)pyrene (50 mg/kg bodyweight dissolved in corn oil, orally) twice weekly for four successive weeks; group III cancer-bearing animals (after 12 weeks of induction) were treated with paclitaxel (33 mg/kg bodyweight, i.p.) once weekly for 4 weeks; group IV cancer-bearing animals were treated with paclitaxel along with Withania somnifera (400 mg/kg bodyweight) orally once weekly for 4 weeks; and group V animals constituted the drug control treated with paclitaxel along with W. somnifera. The serum, lung and liver were investigated biochemically for aryl hydrocarbon hydroxylase, gamma-glutamyl transpeptidase, 5'-nucleotidase, lactate dehydrogenase and protein-bound carbohydrate components (hexose, hexosamine and sialic acid). These enzyme activities were increased significantly in cancer-bearing animals compared with control animals. The elevation of these in cancer-bearing animals was indicative of the persistent deteriorating effect of benzo(a)pyrene in cancer-bearing animals. Our data suggest that paclitaxel, administered with W. somnifera, may extend its chemotherapeutic effect through modulating protein-bound carbohydrate levels and marker enzymes, as they are indicators of cancer. The combination of paclitaxel with W. somnifera could effectively treat the benzo(a)pyrene-induced lung cancer in mice by offering protection from reactive oxygen species damage and also by suppressing cell proliferation.

5'-Nucleotidase↗