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 1,477 records · Page 82Linked to original sources
PubMed1988

Mutational specificity of benzo[a]pyrene diolepoxide in monkey cells.

Benzo[a]pyrene diolepoxide (BPDE) is thought to be the major mutagenic and carcinogenic intermediate in benzo[a]pyrene metabolism in mammalian cells. In order to test the mutagenic specificity of this compound in mammalian cells, we have used the pZ189 shuttle vector system to identify and analyze point mutations induced when DNA treated in vitro with BPDE is replicated in monkey cells. We find that point mutations occur almost exclusively at G.C base pairs; G.C----T.A and G.C----C.G transversions and single base pair deletions occur most frequently. This pattern is consistent with the known preferential covalent binding of BPDE to G residues.

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

Influence of benzylisothiocyanate and 13-cis-retinoic acid on micronucleus formation induced by benzo[a]pyrene.

The purpose of this study was to investigate the influence of benzylisothiocyanate (BIT) and 13-cis-retinoic acid (RA) upon the genotoxic potential of benzo[a]pyrene (BaP) to induce micronucleus formation in the bone marrow of mice. Eighty-two male mice were divided into 10 groups. One group served as a negative control (olive oil intubation). Four groups received an oral intubation of various concentrations of BIT (15 to 120 mg/kg) and i.p. injections of BaP (185 mg/kg). Another four groups were treated identically, but received RA (20 to 150 mg/kg) in place of BIT. Finally, one group received only i.p. injection of BaP (185 mg/kg). The results showed that both BIT and RA significantly reduced the frequency of micronucleus formation in the bone marrow of the BaP treated animals. BIT was found to be effective at all the tested concentrations. RA was effective only at three of the four tested concentrations (40, 75 and 150 mg/kg). These findings indicate that both BIT and RA may reduce the genotoxic effects of benzo[a]pyrene in the mice under the test conditions utilized.

Animals↗
PubMed1992

Mechanisms by which benzo[a]pyrene, an environmental carcinogen, suppresses B cell lymphopoiesis.

The capacity for polycyclic aromatic hydrocarbons (PAH) to suppress immune cell function has been well documented. Nevertheless, mechanisms responsible for PAH immunosuppression and potential effects of PAH on lymphocyte development (lymphopoeisis) remain poorly defined. Murine bone marrow cultures were used in the present studies to determine if and by what mechanism(s) benzo[a]pyrene (B[a]P), a prototypic and highly carcinogenic PAH, suppresses B cell lymphopoiesis. Emphasis was placed on similarities between the processes leading to transformation and immunosuppression and on a possible role for programmed cell death (apoptosis) in B[a]P lymphotoxicity. Data presented herein indicate that: (1) B[a]P suppresses B cell lymphopoiesis in bone marrow cultures at extremely low concentrations (10(-8) M); (2) benzo[e]pyrene, the relatively noncarcinogenic congener of B[a]P, is approximately 1000 times less potent than B[a]P in suppressing B cell lymphopoiesis; (3) bone marrow cells from PAH-resistant DBA/2 mice are less sensitive to B[a]P than cells from C57BL/6 mice; (4) B[a]P induces preB cell apoptosis; and (5) alpha-naphthaflavone, an inhibitor of Ah-receptor dependent, P450 isoenzyme activity, blocks B[a]P-mediated preB cell apoptosis and inhibits B[a]P-dependent suppression of lymphopoiesis. The results support the hypothesis that B[a]P suppression of B cell lymphopoiesis is mediated at least in part by the induction of programmed cell death and that the Ah receptor and/or P450 isoenzymes are involved in this process. The results suggest the potential for PAH to affect development of the B lymphocyte repertoire.

Animals↗
PubMed1995

Induction and repair of benzo[a]pyrene-DNA adducts in C57BL/6 and BALB/c mice: association with aging and longevity.

In this study, we employed the sensitive 32P-postlabeling assay to assess the influence of age on the formation and disappearance of benzo[a]pyrene (B[a]P) DNA adducts in six organs of two different mouse strains with different life spans, C57BL/6ByJ (C57BL/6) and BALB/cByJ (BALB/c). Following a single, intraperitoneal treatment with 50 mg B[a]P per kg of bodyweight, maximum formation of the major B[a]P-derived adduct, trans-(7R)-N2-[10-(7 beta,8 alpha, 9 alpha-trihydroxy- 7,8,9,10)-tetrahydrobenzo[a]pyrene]-yl-deoxyguanosine (BPDE-N2-dG), appeared to be age- and organ-dependent; minor differences were observed for the same organs between the two mouse strains. The maximum formation of BPDE-N2-dG in the various organs from young and old mice differed by a factor of 2-4 and was two- to eightfold lower in organs from old mice as compared to young mice. The removal of BPDE-N2-dG, up to 7 days after the treatment, was apparently age- and strain-dependent; non-significant differences were observed for organs within strains at each age studied. In young C57BL/6 mice, which have a greater life expectancy than BALB/c, the rate of disappearance of BPDE-N2-dG was significantly higher in liver and heart as compared to young BALB/c. At the older age a decrease in the rate of BPDE-N2-dG disappearance was observed more frequently, and to a relatively greater extent, in organs from C57BL/6 mice as compared to BALB/c mice. These results are discussed in relation to the differences in life spans and the incidence of pathological lesions between the two strains of mice.

Aging↗
PubMed1982

Measurements of benzo(a)pyrene in the city of Bombay for the evaluation of carcinogenic risk.

Cigarette smoking, environmental chemicals and ionizing radiations are the three factors known to cause cancer in human beings. The relative importance of each of these is being constantly evaluated. There is an urgent need to monitor the environmental carcinogens on a large scale to assess the role of environmental chemicals in the incidence of cancer in human populations. Polycyclic aromatic hydrocarbons (PAH) are released into the atmosphere as a result of fossil fuel combustion and some of the PAH (e.g. benzo(a)pyrene) are recognised carcinogens. Measurement of benzo(a)pyrene in urban, suburban and rural regions of Bombay is carried out in order to evaluate the possible correlation with lung cancer incidence among different population groups. The variations in the concentration at the three sampling locations are discussed. The wide differences in the concentration at different locations seem to be very suitable for epidemiological investigations.

Air Pollutants↗
PubMed1985

DNA damage by benzo[a]pyrene in the liver of mosquito fish Gambusia affinis.

Exposure of Gambusia affinis to water containing different concentrations of benzo[a]pyrene (BaP) causes an increase in benzo[a]pyrene monooxygenase (BPMO) activity which reaches a maximum on the second day. Concomitantly, the DNA is altered in such a way that nuclease S1-sensitive sites (SSS) become measurable. The size distribution of liver DNA treated with nuclease S1 in control fish shows two populations of DNA by length, with means of 30 X 10(6) and 60 X 10(6) Daltons, respectively. In fish treated with 100 ppb BaP, the population with longer molecules of DNA disappears and shorter molecules increase in number. This may be explained in terms of the introduction of an additional 0.31-0.46 DNA nicks per control DNA molecule caused by metabolically activated BaP derivatives.

Animals↗
PubMed1994

Fluorochromes with long-lived fluorescence as potential labels for pulsed laser immunocytofluorometry: photophysical characterization of pyrene derivatives.

An apparatus for laser-induced time-resolved fluorescence measurements, in conjunction with pyrene derivatives endowed with long-lived excited singlet states, was employed for immunocytofluorometric measurements. N-(1-pyrene)maleimide, 1-pyrenesulfonyl chloride and 1-pyreneisothiocyanate were conjugated with immunoglobulin, antimouse-IgG, and the fluorescence decays of both free and conjugated forms were investigated. Bi-exponential decays were obtained in all cases with time constants of the short-lived component in the range 3-4.7 ns and the long-lived one in the range 20-55 ns. Only the spectral distribution of the two components is essentially affected upon conjugation. The persistence of the long-lived component, well above the lifetime of autofluorescence, and of the antibody specificity, as shown by immunodiffusion tests, upon conjugation indicates that this technique could be advantageously adopted in immunocytofluorometry.

Animals↗
PubMed1985

Host-mediated mutagenicity experiments with benzo[a]pyrene and two of its metabolites.

Benzo[a]pyrene (BP) and two of its major metabolites, the ultimate mutagen BP-4,5-oxide and the proximate mutagen trans-7,8-dihydro-7,8-dihydroxybenzo[a]pyrene (BP-7,8-diol) were investigated for mutagenicity in Salmonella typhimurium TA1538, TA98 and TA100 using an intrasanguineous host-mediated assay. BP and BP-4,5-oxide were not mutagenic under any experimental conditions. BP-7,8-diol was inactive with the strain TA1538 but was mutagenic with the strains TA98 and TA100. The effect was potentiated by pretreatment of the host mice with the cytochrome P-450 inducer 5,6-benzoflavone. We conclude: (i) one of the reasons for the observed insensitivity of the intrasanguineous host-mediated assay towards BP is that BP-4,5-oxide, which contributes to the microsome-mediated mutagenicity of BP, is inactive in the host-mediated assay; (ii) the finding that BP-7,8-diol is mutagenic in the host-mediated assay demonstrates that the lack of mutagenicity of BP is not intrinsic; (iii) the potentiated mutagenicity after treatment of the hosts with 5,6-benzoflavone suggests that cytochrome P-450 is more important in the activation of BP-7,8-diol in this system than other enzymes (e.g. prostaglandin synthase) that can also activate this compound in vitro.

Animals↗
PubMed1988

Antimutagenic effects of several subfractions of extract from wheat sprout toward benzo[a]pyrene-induced mutagenicity in strain TA98 of Salmonella typhimurium.

The aqueous extract from wheat sprouts contains some antimutagenic factor(s). The factor(s) abolish(es) the activity of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) in the S9 fraction from Aroclor-treated rat livers and also inhibit(s) the mutagenic activity of benzo[a]pyrene (B(a)P) in the Ames test. The extract (fraction S30) was subjected to initial fractionation by thermal treatment, 3 24-h cycles of dialysis and ultrafiltration. The antigenotoxic activity of fraction S30 amounted to 98% and was unchanged by thermal treatment (100 degrees C, 10 min). Both the dialysate and the dialysis fluid inhibited the mutagenic effect of B(a)P by 48.4 and 48% respectively. The microsomal subfraction inhibited the mutagenicity only in 10%, and the postmicrosomal subfraction in 68%. It is concluded that the extract from wheat sprouts contains at least 2 heat-resistant compounds (or groups of compounds) located within the cell cytosol and showing antimutagenic activity: one group is of low molecular weight and another of high MW. Alternatively, low-molecular compounds could either be free or bound to high-molecular compound(s).

Animals↗
PubMed1991

Differences in the rate of DNA adduct removal and the efficiency of mutagenesis for two benzo[a]pyrene diol epoxides in CHO cells.

The initiation of carcinogenesis by carcinogens such as 7r,8t-dihydroxy-9,10t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-I) is thought to involve the formation of DNA adducts. However, the diastereomeric diol epoxide, 7r,8t-dihydroxy-9,10c-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE-II), also forms DNA adducts but is inactive in standard carcinogenesis models. We have measured the formation and loss of DNA adducts derived from BPDE-II in a DNA-repair-proficient line of Chinese hamster ovary (CHO) cells, AT3-2, and in two derived mutant cell lines, UVL-1 and UVL-10, which are unable to repair bulky DNA adducts. BPDE-II adducts were lost from cellular DNA in AT3-2 cells with a half-life of 13.8 h; this was about twice the rate found for BPDE-I adducts. BPDE-II adducts were also lost from DNA in UVL-1 and UVL-10 cells, but at a much slower rate. When purified DNA was modified in vitro with BPDE-II and then held at 37 degrees C, DNA adducts were removed at a rate identical to that seen in UVL-1 and UVL-10 cells, suggesting that the loss in these cells was not due to enzymatic DNA-repair processes but to chemical lability of the adducts. Mutant frequencies at the APRT and HPRT loci were measured at BPDE-II doses that resulted in greater than 20% survival, and were found to increase linearly with dose. In the DNA-repair-deficient cells, the HPRT locus was moderately hypermutable compared with AT3-2 cells (about 5-fold); the APRT locus was extremely hypermutable, giving about 25-fold higher mutant fractions in UVL-1 and UVL-10 than in AT3-2 cells at equal initial levels of binding. When we compared the mutational efficiency of BPDE-II at both loci in AT3-2 cells (the mutant frequency in mutants/10(6) survivors at a dose that resulted in one adduct per 10(6) base pairs) with our previous studies of BPDE-1, we found that BPDE-II was 4-5 times less efficient as a mutagen than BPDE-I. This difference in mutational efficiency could be explained in part by the increased rate of loss of BPDE-II adducts from the cellular DNA, part of which was due to an increased rate of enzymatic removal of these lesions compared with the removal of BPDE-I adducts.

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

Single-base deletion induced by benzo[a]pyrene diol epoxide at the adenine phosphoribosyltransferase locus in human fibrosarcoma cell lines.

Benzo[a]pyrene diol epoxide (BPDE), a metabolic product of benzo[a]pyrene, is one of the most widely distributed environmental carcinogens. In this study, we demonstrate that BPDE produces a dose-dependent increase in the frequency of APRT gene reversion in the APRT-deficient cell line, HTD114, which contains single nucleotide insertions at different positions in each APRT allele. The highest reversion frequency observed after BPDE exposure was 3.3 +/- 0.9 x 10(-5), at least 10(3)-fold greater than the spontaneous frequency. Reversion of either mutant allele was observed to be a consequence of a frame-restoring loss of a single nucleotide. A similar frequency of BPDE-induced reversion at APRT also was observed in a cell line containing only one type of the mutant alleles of HTD114, thus eliminating the possibility that gene conversion plays a major role in APRT gene reversion in HTD114 cells. Therefore, the data demonstrate that BPDE can function as an effective frameshift mutagen in human cells.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMedDate not supplied

Differential induction of sister-chromatid exchanges by benzo[a]pyrene in variant mouse hepatoma cells.

Two variant mouse hepatoma cell lines had been separated from a parent cell line, Hepa-1c1c7, by fluorescence activated cell sorting. Earlier metabolic studies had shown that variant TAOc1BPrc1 was more active in the metabolism of the indirect carcinogen benzo[a]pyrene than was variant BPrc1. In an extension of these studies, the relationship between the metabolic capabilities of these two cell lines and the induction of sister-chromatid exchanges by B[a]P was investigated. It was observed that TAOc1BPrc1 yielded a significant dose-dependent increase in the induction of SCE by B[a]P whereas BPrc1 did not show a response significantly greater than control. Metabolic results indicated that the induction of SCE in TAOc1BPrc1 was due to the production of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by this variant. This metabolite did not appear to be produced by BPrc1. Furthermore, TAOc1BPrc1 required only 40 nM B[a]P to induce a 2-fold increase in SCE frequency. This concentration is considerably lower than that required to elicit a similar response in other reported cell lines. To our knowledge, this is the first report of the use of a mouse hepatoma cell line for determining the relationship of metabolic capability to the induction of SCE.

Animals↗
PubMed1987

Effect of in vivo administration of the carcinogen benzo(a)pyrene on interleukin-2 and interleukin-3 production.

B6C3F1 mice were exposed to the environmental carcinogen benzo(a)pyrene, a well known immunosuppressant. The ability of isolated splenocytes to produce and respond to the immunoregulatory molecules interleukin-2 (IL-2) and interleukin-3 (IL-3) was measured. Significant suppression by BaP of IL-2, but not IL-3, production following BaP exposure was observed. Further, exogenous recombinant IL-2 reconstituted the ability of splenocytes from benzo(a)pyrene treated mice to generate IgM antibody producing cells to the T-dependent antigens of sheep red blood cells. These results indicate that one of the cellular target(s) of BaP induced immunosuppression may be the mechanism(s) responsible for lymphokine production and regulation by activated T cells.

Animals↗
PubMed1984

Prostaglandins and mutagenesis: prevention and/or reversibility of genetic damage induced by benzo (a) pyrene in the bone marrow cells of mice by prostaglandin E1.

Prostaglandin E1 and thromboxane A2 (PGE1 and TXA2) have been proposed to bind to DNA, regulate gene action and prevent mutagenesis. Benzo (a) pyrene (BP) is a known mutagen and tumor promotor. BP-induced damage to the bone marrow cells of mice was prevented and/or reversed by PGE1 and by colchicine, an agent which may enhance PGE1 synthesis and TXA2 synthesis or action. PGF2 alpha did not have any action. Imidazole, a selective TXA2 synthesis inhibitor, enhanced the mutagenic action of benzo (a) pyrene. These results lend support to the concept that an altered PG system may have a role in the pathogenesis of mutagenesis and carcinogenesis.

Alprostadil↗
PubMed1987

The relationship between benzo(a)pyrene diol-epoxide-DNA adducts and mutagenicity in the CHO/HPGRT assay.

We have studied the relationship between DNA adducts in Chinese hamster ovary (CHO) cells and mutagenicity as determined in the CHO/hypoxanthine-guanine phosphoribosyltransferase assay. The cells were treated with benzo(a)pyrene 7,8-diol (BP-diol) in the presence of a bioactivation system, S9 mix. DNA binding by bioactivation of BP-diol with S9 mix occurred with both stereoisomers of benzo(a)pyrene diol-epoxide (BPDE) in approximately equal amounts. The number of BPDE-DNA adducts (21-260 adducts/10(6) nucleotide base pairs) increased with increasing treatment concentrations of BP-diol (1.4-7.0 microM). A linear relationship was observed between the number of BPDE-DNA adducts and mutagenicity (89-605 mutants/10(6) cloneable cells) over the concentration range of BP-diol assayed.

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

Effects of dietary cabbage, Brussels sprouts, Illicium verum, Schizandra chinensis and alfalfa on the benzo[alpha]pyrene metabolic system in mouse liver.

Male C57B16 mice were fed on diets containing either 20% cabbage, 20% Brussels sprouts, 20% alfalfa, 5% Schizandra chinensis or 5% Illicium verum (two Chinese medicinal herbs) or on a chow or purified basal diet for 14 days after a 1-wk equilibration period on the basal diet. Liver microsomal fractions were assayed for cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH) and epoxide hydrolase (EH). Liver microsome-mediated benzo[a]pyrene (BP) metabolism (with and without an EH inhibitor, 1,2-epoxy-3,3,3-trichloropropane) was analysed by HPLC. Liver weights of the animals fed on Brussels sprouts and I. verum were significantly increased compared with those of the animals fed on basal diets. S. chinensis induced a 3-fold increase in cytochrome P-450 (P less than 0.05). Although P-450 induction in the other groups was as high as 1.8-fold (for chow), statistical significance was not established. Chow induced AHH activity 2.2-fold (P less than 0.05), while S. chinensis and alfalfa induced 1.6-fold and 1.7-fold increases, respectively, in AHH activity, although neither increase was statistically significant. EH was stimulated significantly in the following order: I. verum (2.1-fold) greater than chow (1.7-fold) greater than S. chinensis (1.6-fold) greater than Brussels sprouts (1.4-fold). Total levels of BP metabolism and phenol II (primarily 3-hydroxybenzo[a]pyrene) formation were closely associated for each dietary treatment. Total BP metabolism was significantly increased (2.1-fold) in the chow-fed group and increased 1.6-fold in the S. chinensis group (P greater than 0.05). No increase was seen with the other diets. Phenol II formation relative to total metabolites was significantly increased for the S. chinensis and I. verum groups compared to the basal group. Diet-related variations in phenol production relative to total metabolism were eliminated by addition of the EH inhibitor to the incubation media.

Animal Feed↗
PubMed1983

Effects of dietary broccoli and butylated hydroxyanisole on liver-mediated metabolism of benzo[a]pyrene.

Groups of male Wistar rats were given either a basal diet or diets supplemented with 10 or 25% broccoli or 0.8% BHA. Liver fractions were assayed for cytochrome P-450, for aryl hydrocarbon hydroxylase (AHH), glutathione-S-transferase and epoxide hydrolase activities and for benzo[a]pyrene (BaP) metabolism. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of liver microsomes was also performed. Mean relative liver weight in the BHA group was significantly higher than that of the control and 10% broccoli groups but not significantly higher than that of the 25% broccoli group. Gel electrophoresis of liver microsomes indicated a diet-dependent variation in intensity in a band that corresponded in mol wt to those of certain cytochrome P-450s. Diet-dependent increases (20-90% over control) in cytochrome P-450 and in the activities of AHH, glutathione-S-transferase and epoxide hydrolase were observed in livers from rats given broccoli-supplemented diets. Except for AHH activity, such increases also occurred in the group fed BHA. Analysis of BaP metabolites revealed that the proportion of 4,5-diol formed relative to the major diols identified was unchanged in the broccoli- or BHA-treated groups relative to the control group. The proportion of 9,10-diol formed was unchanged in the broccoli-fed groups but was significantly higher in the BHA group than in the control group. The proportion of cis and trans-7,8-diol formed was unchanged in both broccoli-fed groups but was significantly lower in the BHA group. In comparison with the control group, the ratio of phenol I (comprising primarily 9-OH-BaP) to total phenols (primarily 9-OH and 3-OH) was significantly decreased by about 30% in the 25%-broccoli group and by about 70% in the BHA group. Qualitative differences in the phenol-II peak (comprising 3-OH and 7-OH phenols) were also observed between samples from the controls and those of 25%-broccoli- and BHA-fed rats. The implications of these findings are discussed with respect to the effects of broccoli and BHA on benzo[a]pyrene toxicity.

Animals↗