PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Pyrenes”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 55 records · Page 3Linked to original sources
PubMed1995

The oxidation of pyrene and benzo[a]pyrene by nonbasidiomycete soil fungi.

The purpose of this study was to determine the ability of nonbasidiomycete soil fungi to oxidize pyrene (four rings) and benzo[a]pyrene (BaP) (five rings). Fungi were isolated from five different soils in which the polycyclic aromatic hydrocarbon content ranged from 0.8 to 80 micrograms/g dry soil. Approximately 50% of the isolates in all sites were able to oxidize pyrene. The pyrene-oxidizing species belonged to all fungal divisions except basidiomycetes. The most common were Penicillium spp. of the subgenus Furcatum and these dominated the more contaminated soils. Penicillium janthinellum and Syncephalastrum racemosum exhibited the most rapid rates of pyrene oxidation. The major pyrene metabolites were identified by proton NMR and mass spectrometry as 1-pyrenol, 1,6- and 1,8-pyrenediol, and the 1,6-and 1,8-pyrenequinones. A high correlation was found between the ability to oxidize pyrene and BaP. As with pyrene, approximately 50% of the fungal isolates tested oxidized BaP to 9-hydroxy-BaP. Eighty percent of the pyrene-oxidizing strains were also able to metabolize BaP.

Benzo(a)pyrene↗
PubMed2005

Bacillus subtilis is a potential degrader of pyrene and benzo[a]pyrene.

Polycyclic Aromatic Hydrocarbons (PAHs) are a group of compounds that pose many health threats to human and animal life. They occur in nature as a result of incomplete combustion of organic matter, as well as from many anthropogenic sources including cigarette smoke and automobile exhaust. PAHs have been reported to cause liver damage, red blood cell damage and a variety of cancers. Because of this, methods to reduce the amount of PAHs in the environment are continuously being sought. The purpose of this study was to find soil bacteria capable of degrading high molecular weight PAHs, such as pyrene (Pyr) and benzo[a]pyrene (BaP), which contain more than three benzene rings and so persist in the environment. Bacillus subtilis, identified by fatty acid methyl ester (FAME) analysis, was isolated from PAH contaminated soil. Because it grew in the presence of 33 microg/ml each of pyrene, 1-AP and 1-HP, its biodegradation capabilities were assessed. It was found that after a four-day incubation period at 30 degrees C in 20 microg/ml pyrene or benzo[a]pyrene, B. subtilis was able to transform approximately 40% and 50% pyrene and benzo[a]pyrene, respectively. This is the first report implicating B. subtilis in PAH degradation. Whether or not the intermediates resulting from the transformation are more toxic than their parent compounds, and whether B. subtilis is capable of mineralizing pyrene or benzo[a]pyrene to carbon dioxide and water, remains to be evaluated.

Bacillus subtilis↗
PubMed1996

Adjuvant activities of pyrene, anthracene, fluoranthene and benzo(a)pyrene in production of anti-IgE antibody to Japanese cedar pollen allergen in mice.

We have previously demonstrated that pyrene in diesel-exhaust particles (DEP) has an adjuvant activity on immunoglobulin E (IgE) antibody production in mice immunized with Japanese cedar pollen allergen (JCPA) or ovalbumin (OA) intraperitoneally. The present study is concerned with the adjuvant activity in IgE antibody production against JCPA of pyrene or DEP inoculated intranasally in mice. We show that anthracene, fluoranthene and benzo(a)pyrene in DEP have the ability to enhance anti-JCPA IgE antibody production in mice by intranasal immunization. Mice were grouped, immunized with 10 micrograms of JCPA plus 400 micrograms of pyrene, 10 micrograms of JCPA plus 100 micrograms of DEP, 10 micrograms of JCPA plus 2 mg of aluminum hydroxide and 10 micrograms of JCPA alone intranasally 7 times at 2 week intervals. Mice were also grouped, and immunized with JCPA (10 micrograms) plus 40 micrograms of anthracene, JCPA (10 micrograms) plus 400 micrograms of fluoranthene, JCPA (10 micrograms) plus 40 micrograms of benzo(a)pyrene, and JCPA (10 micrograms) plus 400 micrograms of pyrene and JCPA (10 micrograms) alone. We found that the IgE antibody responses to JCPA in mice immunized with JCPA plus pyrene, JCPA plus DEP or JCPA plus the three chemical organic compounds mentioned above were significantly enhanced compared with those immunized with JCPA alone. In addition, when the intraperitoneal macrophages obtained from the normal mice (unimmunized mice) were incubated with pyrene, anthracene, fluoranthene or benzo(a)pyrene in vitro, an enhanced chemiluminescence (CI) response and interleukin-1 alpha (IL-1 alpha) production of the macrophages was observed in each instance. These results suggest that in the production of IgE antibody to JCPA the adjuvancy of polycyclic aromatic hydrocarbons (PAHs) in DEP may be important in an attack of Japanese cedar pollinosis.

Adjuvants, Immunologic↗
PubMed1992

Linoleate-dependent co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol by rat cytosolic lipoxygenase.

1. Co-oxygenation of 14C-labelled benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol was studied in rat lung cytosol, using linoleic acid as a co-substrate. Covalently bound and soluble metabolites were quantified by radiometry and h.p.l.c., respectively. 2. The co-oxygenation resulted in the production of reactive metabolites capable of protein binding as well as a series of soluble derivatives. 3. Co-oxygenation of benzo(a)pyrene yielded primarily a significant amount of benzo(a)pyrene-6,12-dione while benzo(a)pyrene-7,8-dihydrodiol led to a significant amount of benzo(a)pyrene-trans-anti-tetrol. 4. Their production was abolished by addition of 25 microM of the lipoxygenase inhibitor and antioxidant NDGA. 5. It is postulated that the linoleic acid peroxyl radicals, formed by rat lung lipoxygenase, initiate the one-electron oxidation of benzo(a)pyrene to its quinones, and epoxidation of benzo(a)pyrene-7,8-diol to the ultimate carcinogenic benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide.

Animals↗
PubMed1972

Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation and metabolism of epoxides related to benzo(a)pyrene and to 7,8- and 9,10-dihydrobenzo(a)pyrene.

Products that appeared to be mainly benzo[a]pyrene 7,8-oxide and benzo[a]pyrene 9,10-oxide were synthesized and their chemical and biochemical properties were investigated. The oxides were unstable and readily rearranged to phenols. They were converted by rat liver homogenates and microsomal preparations into phenols and dihydrodiols, but glutathione conjugates were not formed in appreciable amounts. The dihydrodiols formed from benzo[a]pyrene 7,8- and 9,10-oxide by rat liver microsomal preparations were identical in their chromatographic and spectrographic properties with dihydrodiols formed when benzo[a]pyrene was metabolized by rat liver homogenates. 9,10-Dihydrobenzo[a]pyrene 7,8-oxide and 7,8-dihydrobenzo[a]pyrene 9,10-oxide were also synthesized. They were converted by rat liver homogenates and microsomal preparations into the related cis- and trans-dihydroxy compounds. Glutathione conjugates were formed from the oxides by rat liver homogenates. Both 7,8- and 9,10-dihydrobenzo[a]pyrene were metabolized by rat liver homogenates to mainly the trans-isomers of the related dihydroxy compounds. In experiments with boiled homogenates, the benzo[a]pyrene oxides were converted into phenols, whereas the dihydrobenzo[a]pyrene oxides yielded small amounts of the related dihydroxy compounds.

Animals↗
PubMed1980

On the effect of cellular nucleophiles on the binding of metabolites of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene to nuclear DNA.

The binding to DNA of products resulting from the further activation of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene and 9-hydroxybenzo(a)pyrene was studied in several incubation systems. In a system containing purified DNA and rat liver microsomes, products of 9-hydroxybenzo(a)pyrene were the predominant binding species. In a system containing isolated rat hepatocytes, the total binding was much lower, and products of trans-7,8-dihydroxy-7, 8-dihydrobenzo(a)pyrene predominated. Both the total amounts and the ratios of the bound species were altered by the addition of various soluble nucleophiles to the incubation system. The binding of 9-hydroxybenzo(a)pyrene to both nuclear and purified DNA was decreased in the presence of "non-specific" protein in the incubate. A decrease in the binding of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene to either purified or nuclear DNA was seen after the addition of active cytosol, but not with protein alone. Either denaturation of the cytosol, or depletion of glutathione by diethylmaleate treatment, partially negated this effect. We conclude that the binding of benzo(a)pyrene metabolites to DNA in the cell is decreased by soluble nucleophiles, and that this trapping of metabolites is selective. 9-Hydroxybenzo(a)pyrene metabolites are removed by non-specific protein binding, whereas removal of trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene metabolites requires higher affinity binding or enzymatic conjugation.

Animals↗
PubMed1981

Mutagenicity of the bay-region diol-epoxides and other benzo-ring derivatives of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene.

The mutagenic activities of dibenzo(a,h)(pyrene, dibenzo(a,i)pyrene, and a total of 11 of their benzo-ring derivatives were evaluated in bacterial and mammalian cells in the absence or presence of a mammalian metabolic activation system. trans-1,2-Dihydroxy-1,2-dihydrodibenzo(a,h)pyrene and trans-3,4-dihydroxy-3,4-dihydrodibenzo(a,i)pyrene, the expected dihydrodiol precursors of bay-region diol-epoxides, were metabolized to products which were more mutagenic to strains TA98 and TA100 of Salmonella typhimurium than were the metabolic products formed from their respective parent hydrocarbons. For each dihydrodiol, replacement of the benzo-ring double bond adjacent to the diol moiety with a single bond resulted in tetrahydrodiol derivatives which could not be metabolically activated, suggesting that one or both diastereomeric bay-region diol-epoxides were the bioactivated metabolites. The authentic bay-region diol-epoxide diastereomers of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene in which the benzylic hydroxyl group and the epoxide oxygen are trans (diol-epoxide 2 series) were highly mutagenic in strains TA98 and TA100 of S. typhimurium and in cultured Chinese hamster V79 cells. Neither diol-epoxide was significantly, if at all, metabolized by epoxide hydrolase. The bay-region diol-epoxide of dibenzo(a,i)pyrene was from 1.5 to 5 times more active as a mutagen than the diol-epoxide of dibenzo(a,h)pyrene, and in strain TA98 of S. typhimurium as well as Chinese hamster V79 cells, it had activity comparable to that of the highly carcinogenic bay-region diol-epoxide of benzo(a)pyrene.

Animals↗
PubMed2005

FIA/MS analysis of temporally ozonated benzo[a]pyrene and pyrene and their reaction products: inhibition of gap junction-mediated intercellular communication.

In this study, the polycyclic aromatic hydrocarbons, benzo[a]pyrene (BaP) and pyrene, were subjected to temporal ozonation. The products from ozonation of 5 mg l(-1) BaP and 5 mg l(-1) pyrene, for varying time intervals (0, 1, 2, 3, 4, 5, 6, 8, 10, 20, and 30 min) were tested for their effects on gap junction-mediated intercellular communication (GJIC) in Clone 9 rat liver cells. Additionally, the ozonation products were also analyzed by flow injection analysis/mass spectrometry (FIA/MS) and the results were compared with the toxicity observed in the GJIC assay. Treatment of the Clone 9 cells with 5 mg l(-1) of ozonated BaP products resulted in a decrease in GJIC that was inversely proportional to the length of ozonation. The products from 1 min of ozonation resulted in a 92% decrease in the rate of GJIC, but with >5 min ozonation, the products did not suppress GJIC. In contrast, pyrene (0.5 mg l(-1)) required >10 min of ozonation to alleviate its effects on GJIC. FIA/MS, using atmospheric pressure chemical ionization (APCI), demonstrated products with higher molecular weights (MW) than their corresponding parent compounds, BaP (MW 252) and pyrene (MW 202). Ozonation of pyrene formed significantly fewer products than BaP. More importantly, pyrene ozonation products were constant from 1 to 10 min, while BaP ozonation products seemed to vary between time intervals. With the longer ozonation times (20 and 30 min), BaP and pyrene formed similar products (m/z peaks 157, 111, and 96). The suppression of GJIC by ozonated products seemed to correlate with oxidation of the aromatic ring framework. Further oxidation (longer ozonation times) to lower MW products correlated with restoration of normal GJIC.

Animals↗
PubMed1986

Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay.

Eight nitropolycyclic aromatic hydrocarbons (PAHs), including 1- and 4-nitropyrene, 1,3-, 1,6- and 1,8-dinitropyrene, 7-nitrobenz[a]anthracene, 6-nitrochrysene and 6-nitrobenzo-[a]pyrene and their parent PAHs were tested fro tumorigenicity in the newborn mouse model by i.p. administration at 1, 8, and 15 days after birth. Both pyrene and 1-nitropyrene induced similar incidences of hepatic tumors in males, yielding a 12-15% and a 21-28% tumor incidence at total doses of 700 and 2800 nmol per mouse, respectively. Liver tumors did not occur in females and the 3-10% lung tumor yield in both sexes was similar to that found in solvent-treated controls. The presumed proximate carcinogen, 1-nitrosopyrene, administered at 700 nmol per mouse, caused liver tumors in 45% of the males and in 9% of the females. 4-Nitropyrene was more tumorigenic than pyrene or 1-nitropyrene; at a dose of 2800 nmol, it induced liver tumors in 83% of the males and 7% of the females, with a lung tumor yield of 38 and 31%, respectively. Female mice treated with 200 nmol of 1,3-, 1,6- or 1,8-dinitropyrene did not develop liver tumors but the hepatic tumor incidence in males was 20, 32 and 16%, respectively, which was significantly greater than that found in mice treated with pyrene. In male mice administered 2800 nmol of benz[a]anthracene, the hepatic tumor incidence was 79%, while treatment with 7-nitrobenz[a]anthracene showed an incidence of only 28%. Similarly, 560 nmol of benzo[a]pyrene caused a 49% liver tumor yield in males while those given 6-nitrobenzo[a]pyrene had a 28% incidence. Treatment with benzo[a]pyrene also induced a 35 and 48% lung tumor incidence in males and females while the comparable values in 6-nitrobenzo[a]pyrene-treated mice were 14 and 2%. Chrysene administered at 2800 nmol per mouse induced hepatic and lung tumors in 41% and 21% of the males, respectively; at the 700-nmol dose, it induced only liver tumors in 29% of the males and in none of the females. In contrast, treatment with 6-nitrochrysene at 700 nmol per mouse resulted in a 76 and 23% hepatic tumor incidence in males and females, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Mutagenic nitrated benzo[a]pyrene derivatives in the reaction product of benzo[a]pyrene in NO2-air in the presence of O3 or under photoirradiation.

In order to clarify the contribution of nitrated products to the direct-mutagenic activity of products of the reactions of benzo[a]pyrene in NO2-air under various conditions, heterogeneous reactions of BaP deposited on filter in the air containing 10 ppm of NO2 have been conducted in dark or under photoirradiation. The reaction products have been analyzed by gas chromatography and mutagenicity of the products fractionated by preparative HPLC was assayed for Salmonella typhimurium strains TA98 and YG1024 in the absence of S9 mix. 3,6-dinitrobenzo[a]pyrene and 1,3-dinitrobenzo[a]pyrene, which are strong direct-acting mutagens, largely contributed to the total direct-acting mutagenicity of the dark reaction products in NO2-air. On the other hand, both the dark reaction in the presence of O3 and the photoreaction in NO2-air resulted in the formation of much smaller amounts of nitrobenzo[a]pyrenes than that observed in the dark reaction in the absence of O3. These results show that the contribution of other direct-acting mutagens to the total direct-acting mutagenicity of the products in these reactions should be considered. Benzo[a]pyrene lactones were identified in a highly mutagenic fraction of the products of the dark reaction in the presence of O3 and photoreaction and a nitrobenzo[a]pyrene lactone was also identified in a highly mutagenic fraction of the dark reaction products in the presence of O3. Nitrated oxygenated benzo[a]pyrene derivatives such as nitrobenzo[a]pyrene lactone were considered to largely contribute to direct-acting mutagenicity of the products of the dark reaction in the presence of O3 and photoreaction.

Air↗
PubMed1984

Fluoranthene and pyrene enhance benzo[a]pyrene--DNA adduct formation in vivo in mouse skin.

Fluoranthene and pyrene are potent cocarcinogens when applied together with benzo[a]pyrene (BaP) on mouse skin. In this study the effect of fluoranthene, pyrene and phenanthrene on the formation of BaP--DNA adducts in mouse skin was investigated. Co-application of either fluoranthene or pyrene with [3H]BaP resulted in an average increase in the level of [3H]BaP--DNA adducts of 56% to 66%, respectively, as compared to [3H]BaP alone. Only minor differences were observed in the ratio of (+/-)anti- to (+/-)synbenzo[a]pyrene diol epoxide--DNA adducts between experimental groups. An average 17% decrease in the formation of [3H]BaP--DNA adducts was observed upon co-application of [3H]BaP on mouse skin with phenanthrene. These data suggest a correlation between the observed increase in tumorigenicity of BaP in the presence of either fluoranthene or pyrene and an increase in the formation of (+/-)anti-benzo[a]pyrene diol epoxide--DNA adducts.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1980

Fungal oxidation of (+/-)-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene: formation of diastereomeric benzo[a]pyrene 9,10-diol 7,8-epoxides.

The filamentous fungus Cunninghamella elegans oxidized (+/-) trans-9,10-dihydroxy-9,10-dihydrobenzo[a]-pyrene to a complex mixture of metabolites which were detected by high-pressure liquid chromatography. Two of the metabolites were identified as (+/-)7 beta, 8 alpha, 9 alpha, 10 beta-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene and (+/-)-7 beta,8 alpha,9 beta,10 alpha-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene. A third product gave absorption and mass spectra consistent with a diol-epoxide structure. Hydrolysis of this compound gave (+/-)-7 beta, 8 alpha, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene as the major identifiable product with a minor unidentified tetraol. Synthetic (+/-)-9 alpha, 10 beta-dihydroxy-7 beta, 8 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene gave the same hydrolysis products and had the same retention time on high-pressure liquid chromatography as did the fungal metabolite. The trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene recovered at the end of the experiment showed no optical activity, indicating that both enantiomers were metabolized by the fungus. the results suggest that C. elegans oxidizes (+/-)-trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene to diastereomeric benzo[a]pyrene 9,10-diol 7,8-epoxides.

Benzopyrenes↗
PubMedDate not supplied

Distribution of benzo[a]pyrene in pregnant rats following inhalation exposure and a comparison with similar data obtained with pyrene.

Eight pregnant rats were exposed, on the 17th day of gestation, for 95 min to a microcondensation aerosol of benzo[a]pyrene at five different atmospheric concentrations between 200 and 800 mg m-3 in a 'head-only' inhalation chamber. Five rats were killed immediately following the exposure and three were killed at 6 h post-dosing. Concentrations of the radiolabel and 'free' benzo[a]pyrene were measured in the individual fetuses and in the maternal blood, fat, kidney, liver and lung. Distribution to the fetus did not appear to be related to its position on the uterine horn and the uptake of benzo[a]pyrene was non-linear with increasing exposure concentrations, which was similar to the observations previously reported for pyrene. The levels of benzo[a]pyrene were much higher in the fetus and, especially, the lung than those observed in the pyrene study; so also were the levels of total metabolites in these tissues, which might, in part, account for the carcinogenic potency of benzo[a] pyrene.

Administration, Inhalation↗
PubMed1993

Involvement of P450 1A1 in benzo(a)pyrene but not in benzo(a)pyrene-7,8-dihydrodiol activation by 3-methylcholanthrene-induced mouse liver microsomes.

Synchronous fluorescence spectrophotometry for benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts was used to study the activation pathway of benzo(a)pyrene in C57BL/6 mice. Benzo(a)pyrene but not benzo(a)pyrene-7,8-diol activation by 3-methylcholanthrene-induced mouse liver microsomes was inhibited by a monoclonal antibody (Mab 1-7-1) against CYP1A1/2 suggesting that 1A1 probably takes part in the first P450 reaction. However, aryl hydrocarbon hydroxylase activity, a classical measure of benzo(a)pyrene metabolism, was not inhibited by the same concentration of Mab 1-7-1. None of the other antibodies used, detecting 2A, 2B, 2C or 2E subfamilies, inhibited the adduct formation. Troleandomycin and gestodene, chemical inhibitors of human 3A4, inhibited benzo(a)pyrene-7,8-diol activation by 3-methylcholanthrene-induced microsomes to some extent only in high concentrations. Although liver microsomes from 3-methylcholanthrene-induced mice catalyzed the formation of BPDE-DNA in vitro clearly more than uninduced microsomes, 3-methylcholanthrene pretreatment in vivo decreased the adduct formation in benzo(a)pyrene-treated mice. These results emphasize the significance of detoxicating and DNA-repairing pathways in vivo. Finally, synchronous fluorescence spectrophotometry for BPDE-DNA measures the end-point of the three-step activation pathway while aryl hydrocarbon hydroxylase measures a one-step hydroxylation. Thus, these methods should be used rather as corroborative than mutually exclusive assays.

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

Pyrene acts as a cocarcinogen with the carcinogens benzo[a]pyrene, beta-propiolactone and radiation in the induction of malignant transformation in cultured mouse fibroblasts; soybean extract containing the Bowman-Birk inhibitor acts as an anticarcinogen.

Pyrene was found to act as a cocarcinogen in the induction of transformation of cultured Balb/c3T3 cells by three different types of carcinogens: a direct acting chemical carcinogen, beta-propiolactone, a chemical carcinogen requiring metabolic activation, benzo[a]pyrene, and a physical carcinogen (60Co) gamma radiation. Since pyrene enhanced transformation in vitro by approximately the same amount for all the carcinogens tested, these results suggest that the carcinogenic action of pyrene is not related to carcinogen metabolism or uptake in vitro. An extract of soybeans containing the Bowman-Birk protease inhibitor was shown to reduce transformation induced by beta-propiolactone, benzo[a]pyrene and gamma-rays, both with and without the cocarcinogenic effect of pyrene, to background levels; the magnitude of the reduction in transformation by the protease inhibitor preparation was unrelated to the concentration of carcinogen. Neither the mechanism for the cocarcinogenic action of pyrene not the anticarcinogenic effect of the soybean extract is known, but several hypotheses are discussed.

Animals↗
PubMed1982

Formation of mutagenic metabolites from benzo(a)pyrene and 2-aminoanthracene by the s-9 fraction from the liver of the Northern pike (Esox lucius): inducibility with 3-methylcholanthrene and correlation with benzo[a]pyrene monooxygenase activity.

The mutagenicity of benzo[a]pyrene and 2-aminoanthracene in the Ames test using the S-9 fraction from the liver of the Northern pike (Esox lucius) was tested. S-9 fractions were prepared both from fish injected intraperitoneally with 3-methylcholanthrene and from control animals. In addition benzo[a]pyrene monooxygenase activity was assayed in the same S-9 fractions used in the Ames test. S-9 fractions from the liver of the Northern pike were found to convert benzo[a]pyrene and 2-aminoanthracene to mutagenic metabolites. The number of revertants obtained was increased 2--4-fold in the case of 2-aminoanthracene and 3--14-fold in the case of benzo[a]pyrene by pretreatment of the pike with a single intraperitoneal injection of 3-methylcholanthrene. This injection also caused a 2--6-fold increase in the benzo[a]pyrene monooxygenase activity of the S-9 fractions used. These increases in mutagenicity and activity of the S-9 fractions used. these increases in mutagenicity and activity occur mainly during the first 4--12 days after the injection, but further small increases are observed for as long as 60 days. A strong positive correlation was found between the benzo[a]pyrene monooxygenase activity of the S-9 fractions used and their ability to give rise to revertants in the Ames test using 2-aminoanthracene or benzo[a]pyrene. This indicates that the major determining factor in the production of reactive metabolites which attack DNA in this in vitro system is the activity of the phase I cytochrome P-450 system.

Animals↗
PubMed1980

Metabolic activation of cyclopenta(cd)pyrene to 3,4-epoxycyclopenta(cd)pyrene by rat liver microsomes.

Cyclopenta(cd)pyrene (CPP), a polycyclic aromatic hydrocarbon without a bay region, is a potent bacterial mutagen. The experiments reported in this paper demonstrate that the major CPP metabolite generated by liver microsomes prepared from either phenobarbital or 3-methylcholanthrene pretreated rats is the optically active trans-3,4-dihydroxy-3,4-dihydrocyclopenta(cd)pyrene. Other experiments indicate that formation of the trans-3,4-dihydrodiol of CPP probably proceeds via enzymatic hydrolysis of 3,4-epoxycyclopenta(cd)pyrene by opening of the O--C(3) bond. (a) The racemic 3,4-epoxycyclopenta(cd)pyrene has been synthesized via the bromohydrin of CPP and shown to hydrolyze primarily to 3,4-dihydrocyclopenta(cd)pyrene-4-one and to mixtures of the trans- and cis-3,4-dihydrodiols. Detection of 3,4-dihydrocyclopenta(cd)pyrene-4-one as the major acid catalyzed rearrangement product indicates the opening of the epoxide at the C(3) position to yield a carbonium ion followed by an NIH shift. (b) The synthetic epoxide is potently mutagenic to bacteria with a similar spectrum of mutagenicity against Salmonella typhimurium strains carrying base-pair substitution or frameshift mutations as was seen with CPP in the presence of liver enzymes. These results indicate that 3,4-epoxycyclopenta(cd)pyrene is the major microsomal and mutagenic metabolite of CPP.

Animals↗