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 127 records · Page 7Linked to original sources

PubMed1992

The co-carcinogen benzo[e]pyrene increases the binding of a low dose of the carcinogen benzo[a]pyrene to DNA in Sencar mouse epidermis.

The mechanism of the co-carcinogenic activity of benzo[e]pyrene (BeP) was investigated by determining the effects of BeP on the binding of the carcinogen benzo[a]pyrene (BaP) to DNA in Sencar mouse epidermis. The dose of BaP used was 20 nmol/mouse, a dose which is not carcinogenic in a single application but is carcinogenic after multiple treatments such as those in the BaP-BeP co-carcinogenesis experiments described by Van Duuren and Goldschmidt (J. Natl. Cancer Inst., 56, 1237, 1976). After 3 h of exposure to [3H]BaP and BeP at BaP:BeP dose ratios of 1:3 and 1:10, [3H]BaP-DNA adducts in both BeP-treated groups were lower than in an acetone-BaP control group. After 12 and 24 h of exposure, the BaP-BeP (1:10) group contained 19% and 33% higher [3H]BaP-DNA adduct levels than the control. In the BaP-BeP (1:3) group, the amount of [3H]BaP-DNA adduct levels was higher than the control after 12 h. BeP co-treatment with either [3H]BaP-7,8-dihydrodiol or anti-[3H]BaPDE had no effect on the amount of BaPDE-DNA adducts present. These results demonstrate that the co-carcinogen BeP increases the amount of a low dose of BaP that binds to mouse epidermal DNA and indicate that the increase in BaP-DNA adducts results from increased metabolism of BaP to the proximate carcinogen BaP-7,8-dihydrodiol.

Animals↗

PubMed1982

Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.

We have determined the spectrum of base-pair substitution mutations induced in the lacI gene of a uvrB- strain of Escherichia coli by two polycyclic aromatic hydrocarbons--(+/-)7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE), and 3,4-epoxycylopenta[cd]pyrene (CPPE). Approximately 10% of all lacI mutations induced by either BPDE or CPPE are nonsense mutations, suggesting that base-pair substitutions are a large fraction of the mutational events induced by these agents in the uvrB- bacteria. Both carcinogens specifically induced the G . C leads to T . A and, to a lesser extent, the A . T leads to T . A transversions. One possible mechanism for transversion induction at G . C sites by BPDE might involve carcinogen binding to the exocyclic amino group of guanine in the template strand followed by a rotation of the modified base around its glycosylic bond from the anti to the syn conformation. This could allow specific pairing of modified bases with an imino tautomer of adenine.

Benzopyrenes↗

PubMed1992

Peroxidase-mediated glutathione conjugation of benzo[a]pyrene-7,8-dihydrodiol is enhanced by benzo[a]pyrene phenols in vitro.

We reported previously that glutathione (GSH) is oxidized by peroxidases to a thiyl radical that can react with a number of chemicals, including the penultimate carcinogenic metabolite benzo[a]pyrene-7,8-dihydrodiol (7,8-B[a]PD), to give GSH conjugates. Here, we report that phenolic metabolites of benzo[a]pyrene (B[a]P) enhance the peroxidase-mediated formation of glutathione conjugates of 7,8-B[a]PD. The GSH conjugation of 7,8-B[a]PD in a horseradish peroxidase/peroxide system was increased over control values as follows: 9-OH-B[a]P by 4-fold, 7-OH-B[a]P by 3-fold, 1-OH-B[a]P by 2-fold. In contrast 3-OH-B[a]P was ineffective. A phenolic derivative of another polycyclic aromatic hydrocarbon (PAH), benz[a]anthracene, also enhanced GSH conjugation of 7,8-B[a]PD. The enhancement was dependent upon the presence of the phenol, horseradish peroxidase and peroxide. The phenolic compounds, including 3-OH-B[a]P, were also efficient reducing cofactors for the peroxidase. With the exception of 3-OH-B[a]P, the phenolic metabolites of PAH enhanced peroxidase-mediated formation of thiyl radical as detected by electron spin resonance spectrometry. Since both phenols and dihydrodiols are metabolites of B[a]P catalyzed by the cytochromes P450 system, enhancement of peroxidase-dependent 7,8-B[a]PD-GSH conjugation by phenols suggests a possible interaction between peroxidases and cytochromes P450 systems. This interaction may contribute to the detoxication of the penultimate carcinogenic PAH-dihydrodiols and other chemicals.

Benzo(a)pyrene↗

PubMed1981

The uptake and release of benzo[a]pyrene and benzo[e]pyrene in vitro by Syrian hamster embryo cells as a function of serum concentration.

A quantitative study on the in vitro uptake of benzo[a]pyrene (B[a]P) and benzo[e]pyrene (B[e]P) by Syrian hamster embryo cells and the induction of sister chromatid exchange (SCE) has been carried out. The amounts of B[a]P and B[e]P taken up by the cells decreases as does the induction of SCEs by B[a]P when the concentration of serum in the culture medium increases. It appears that serum prevents (B[a]P or B[e]P uptake. We have observed no significant differences between the two hydrocarbons regarding uptake by cells; chromatographic results show however that B[a]P is metabolized by these cells, while B[e]P is not. Our results suggest that serum inhibits B[a]P and B[e]P uptake and hence decreases the number of SCEs.

Animals↗

PubMed1982

Glutathione conjugation and DNA-binding of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in isolated rat hepatocytes.

Isolated rat liver hepatocytes, previously depleted of glutathione (GSH) by treatment with diethylmaleate, were allowed to incorporate [3H]glycine into their GSH. Incubation of 3H-labelled cells with 14C-labelled (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene ((+/-)-BP-7,8-dihydrodiol) or (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene ((+/-)-BPDE) revealed the formation of double labelled products. This together with evidence from amino acid analysis indicates formation of GSH-conjugates of the highly carcinogenic BP-derivatives. Incubation of hepatocytes isolated from 3-methylcholanthrene (MC) treated rats with 3H-labelled (+/-)-BP-7,8-dihydrodiol or (+/-)-BPDE resulted in binding of radioactivity to DNA. Reduction of the intracellular level of GSH to approximately 40% of the normal level resulted in an approximate 2-fold increase in the DNA-binding of either substrate. In addition there was a concurrent decrease in the amount of GSH-conjugates formed. These data clearly demonstrate that GSH participates in conjugation reactions with carcinogenic (+/-)-BP-7,8-dihydrodiol and (+/-)-BPDE and that the intracellular level of GSH is important in preventing reactive intermediates from reacting with the DNA in intact cells.

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

PubMed1984

Benzo[e]pyrene-induced alterations in the binding of benzo[a]pyrene to DNA in hamster embryo cell cultures.

Benzo[e]pyrene (B[e]P), a weakly carcinogenic polycyclic aromatic hydrocarbon (PAH) modifies tumor induction in mouse skin and the induction of mutation in mammalian cells by carcinogenic PAH. To determine how B[e]P alters the metabolic activation of the carcinogen benzo[a]pyrene (B[a]P), early passage Syrian hamster embryo cell cultures were exposed to [3H]B[a]P or [3H]trans-7,8-dihydro-7,8-dihydroxyB[a]P (B[a]P-7,8-diol) in the presence of various concentrations of B[e]P for 24 h. The DNA was isolated, degraded to deoxyribonucleosides and the B[a]P-deoxyribonucleoside adducts were analyzed by h.p.l.c. As the dose of B[e]P increased, the amount of B[a]P bound to DNA decreased and the ratio of anti-B[a]P-7,8-diol-9,10-epoxide (B[a]PDE)-deoxyguanosine adduct to syn-B[a]PDE-deoxyguanosine adduct decreased. B[e]P treatment inhibited the binding of B[a]P-7,8-diol to DNA to a greater extent than it inhibited the binding of B[a]P and decreased the ratio of anti- to syn-B[a]PDE-deoxyguanosine adducts formed from the 7,8-diol. These results indicate that B[e]P decreases the activation of B[a]P to DNA-binding intermediates in these cells; especially the oxidation of B[a]P-7,8-diol to a diol-epoxide. The B[e]P-induced alterations in the ratio of DNA adducts formed from the syn- and anti-isomers of B[a]PDE suggest that B[e]P selectively inhibited certain pathways of metabolic activation of B[a]P. Thus, B[e]P-induced modifications in the biological activity of PAH may result from alteration in both the amounts and the relative proportions of various isomeric forms of the ultimate carcinogenic metabolites formed from PAH.

Animals↗

PubMed1984

Metabolism of benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide to protein-binding products and glutathione conjugates in isolated rat hepatocytes.

Isolated hepatocytes from 3-methylcholanthrene (MC)-treated rats metabolized trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol) and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) to water soluble conjugates including glutathione (GSH) conjugates. Under the conditions employed 35% of total water soluble products derived from BP-7,8-diol could be accounted for by GSH conjugates. The corresponding figure for anti-BPDE was estimated to be greater than or equal to 80%. Isolated hepatocytes metabolized BP-7,8-diol and anti-BPDE to GSH conjugates at maximal rates of 0.5 and 9 nmol per 10(6) cells per min, respectively. Thus, identifying the rate limiting step in the reaction sequence as the metabolism of BP-7,8-diol to the GSH conjugating intermediates. In addition to the direct conjugation of anti-BPDE with GSH, anti-BPDE but not the corresponding BP-tetraols, was further metabolized to reactive intermediates that subsequently bound to cellular proteins or reacted with GSH forming water soluble conjugates. The identity or identities of these novel reactive intermediates is discussed.

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

PubMed1987

Binding of benzo[a]pyrene metabolites in the rat intestinal lumen by magnetic polyethyleneimine microcapsules following an intragastric dose of [14C]benzo[a]pyrene.

Semi-permeable magnetic polyethyleneimine (PEI) microcapsules have been developed to trap carcinogens and their metabolites in vivo and their time-dependent binding of a model carcinogen, [14C]benzo[a]pyrene [( 14C]BaP), is studied within the intestinal lumen. Overall, approximately 0.5% of an intragastric BaP dose was bound by these microcapsules recovered from faeces with specific binding of metabolites (nmol/10(6) recovered microcapsules) being similar in the 0-24-h and 24-48-h periods, but approximately 10-fold lower in the 48-72-h period. Successive extractions of microcapsules with ammoniacal methanol, 2.5 N HCl, methanol and dimethylsulfoxide released approximately 60% of bound radiolabeled and the unextracted radiolabel was presumed to have been bound covalently. By contrast, greater than 90% of bound radiolabel was extractable from the faeces of the treated animals and from microcapsules treated in vitro with [14C]7,8-dihydroxy-9,10-epoxytetrahydrobenzo[a]pyrene (BaPDE), indicating that the in vivo microcapsule-bound metabolites were not derived either from adsorbed faecal material or from [14C]BaPDE formed in situ. A time-dependent appearance of BaP 3,6-dione was found. Also the qualitative and quantitative patterns of metabolites trapped by microcapsules, as assayed by h.p.l.c., were consistent only with a unique set of BaP metabolites being bound within the intestinal lumen. Hence these carcinogen-binding microcapsules can be used to investigate the in situ formation of carcinogen metabolites within the intestinal tract.

Animals↗

PubMed1988

Persistence of benzo[a]pyrene and 7,8-dihydro-7,8-dihydroxybenzo[a] pyrene in Fischer 344 rats: time distribution of total metabolites in blood, urine and feces.

A comparison of the rates of elimination of [3H]benzo[a] pyrene (BaP) and 7,8-dihydro-7,8-diol-[3H]benzo[a]pyrene (BPD), after subcutaneous injection into Fischer 344 rats, shows they are both eliminated at about the same rates and with the same pattern over at least 7 days post-exposure. The end-rate of combined urinary and fecal excretion was approximately 40 nmol/day. About 20% of the injected BaP and approximately 3% of the injected BPD remained at the site of injection for at least 9 days. The remainder was distributed throughout the animal. If the rate of excretion continued at the observed steady-state rates, the BaP and BPD could persist for up to 40 days for each milligram of injected substance. The concentration of excretion products were highest during day 1 and day 2 following exposure, decreased exponentially to a concentration of approximately 0.5 microM (mixed metabolites) by day 5 following exposure, and then continued to be excreted at that rate. Feces contained the highest total amounts of radioactivity, which were approximately 2- to 4-fold higher than the amounts in urine and approximately 15- to 50-fold higher than in total blood. The conversion of organic 3H to 3H2O during the experimental period indicates that whole-body phenol(quinone) formation was significant for BaP metabolism, but was much less for BPD metabolism. When BaP was injected, both blood and urine contained water-soluble, volatile tritium counts (3H2O). Injection of BPD resulted in volatile 3H2O in urine but not in blood. The persistence of BaP and BPD metabolites in skin, blood, urine and feces compartments indicates there is a substantial reservoir of the chemical(s) that could be used to replenish repaired or discarded DNA adducts.

Animals↗

PubMed1989

Wheat bran and the induction of intestinal benzo(a)pyrene hydroxylase by dietary benzo(a)pyrene.

The mucosa of the intestine responds to polycyclic aromatic hydrocarbons (PAH) with the rapid induction of benzo(a)pyrene hydroxylase (BPH). Studies were conducted to determine if dietary fiber would reduce exposure of the intestine to dietary benzo(a)pyrene (BP) as indicated by intestinal BPH activity. In all studies, female Sprague-Dawley rats were fed a fiber-free purified diet for 7 d, whereupon they were switched to experimental diets for 48 h. After 48 h their small intestinal mucosa was assayed for BPH activity. Diets for the initial study contained 0, 100, 400, 800, or 1200 mg BP/kg diet, each with and without 10% soft white wheat bran. Enzyme induction with 100 and 400 mg BP/kg diet was partially inhibited by bran, but with higher concentrations of BP there was no protective effect. The inhibition in BP-induced intestinal BPH activity was observed with 10% wheat bran but not with 3.3 or 6.6%. Subsequent studies showed no significant inhibition in BPH induction with cellulose or lignin, whereas all forms of wheat bran (hard red, soft white, or finely ground soft white) caused significant inhibition. In the final study, a diet containing charcoal-broiled beef, a known source of PAH, was compared with diets containing raw beef or soybean protein, each with and without 10% soft white wheat bran. BPH activity remained low with raw beef and soybean protein whether or not fiber was added. However, intestinal BPH activity was raised ninefold by charcoal-broiled beef. The addition of bran reduced BPH activity to 65% of that observed with the fiber-free, charcoal-broiled beef diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[Benzo(a)pyrene pretreatment of Drosophila simulans mutant strain results in the induction of aberrant isoform of cytochrome P-450 with increased capacity to metabolize benzo(a)pyrene].

The basal level of benzo(a)pyrene monooxygenase, epoxide hydrolase and glutathione S-transferase activity as well as the content of cytochrome P-450 were found the same in both compared benzo(a)pyrene (BP) sensitive D. simulans strain 364yv and BP-resistant wild one (Turku). Phenobarbital pretreatment resulted in the same increase level of these enzyme activities in both strains. BP-pretreatment of 364yv flies decreased the amount of the cytochrome P-450 but raised up the turnover of BP per molecule of cytochrome P-450. SDS-polyacrylamide gel electrophoresis of the microsomal proteins from BP-pretreated 364yv flies (but not from Turku) showed an increased hemoprotein content in the 56000 band. The relationship between BP-sensitivity of the strain 364yv and BP-induced aberrant isoform of the cytochrome P-450 has been discussed.

Animals↗

PubMed1990

In vivo DNA adduct formation by benzo(a)pyrene in mouse and rat epidermal and dermal fibroblasts after topical application of an initiating dose of benzo(a)pyrene.

In vivo adduct formation by benzo[a]pyrene (BP) has been compared in mouse and rat epidermal keratinocytes and dermal fibroblasts after topical application of an initiating dose of carcinogen. The BP-DNA adducts were analyzed by chromatography and acid hydrolysis of BP-deoxyribonucleoside adducts to BP-tetrols. BP was dissolved in acetone and applied, at similar doses per unit area (100 nmol/mouse and 240 nmol/rat), to 50-day-old Swiss mice and 35-day-old Wistar rats. Epidermal and dermal cells were isolated twenty four hours later. Reverse-phase HPLC of BP-deoxyribonucleoside adducts demonstrated the presence of three BP-deoxyribonucleosides adducts in mouse epidermal cells and one in mouse dermal cells. An unknown product (0.13 and 0.04 pmol/mg mouse epidermal and dermal cell DNA respectively) eluted before the BP-7,10/8,9-tetrol marker, at same relative position as 9-OH-BP-DNA adduct. The major adduct formed in mouse epidermal keratinocytes and dermal fibroblasts was dGuo modified by (+)-anti-BPDE and accounted for more than 70% of the adducts. Acid hydrolysis of the individual BP-DNA adducts was used to identify the BP-DNA adducts formed in mouse epidermal and dermal cells as anti- and syn-BPDE-dGuo. Twenty four hours after topical application of BP, the total levels of modified deoxyribonucleosides and (+)-BPDE-dGuo were 3 times greater in mouse epidermal cells than in dermal cells. The ratios of anti-BPDE to syn-BPDE was 17:1 and 12:1 in mouse epidermal and dermal cells DNA, respectively. This work provides the evidence that, at an initiating dose, 3H modified deoxyribonucleosides of rat epidermal keratinocytes and dermal fibroblasts are not detectable. This may be essential for the resistance of rat skin to the carcinogenic action of benzo[a]pyrene.

Administration, Topical↗

PubMed1989

[Immune response to benzo(a)pyrene in rabbits immunized with a conjugate of benzo(a)pyrene-albumin, synthesized in the microsomal monooxygenase system of the liver].

The feasibility of obtaining a conjugated benz(a)pyrene-protein antigen in the liver cytochrome P-450 system was studied. Covalent binding of benz(a)pyrene (BP) to albumin was performed with the use of liver microsomal fractions of 3-methylcholanthrene-induced rabbits. It was demonstrated that BP oxidation in liver microsomes is accompanied by covalent binding of [14C]BP to exogenous rabbit albumin. Immunization of rabbits with the obtained conjugate results in the development of a specific immune response to BP, and the appearance of specific antibodies and lymphocytes specifically binding [14C]BP in the blood.

Albumins↗

PubMedDate not supplied

Epidermis: the major site of cutaneous benzo(a)pyrene and benzo(a)pyrene 7,8-diol metabolism in neonatal BALB/c mice.

The metabolism of benzo(a)pyrene (BP) and benzo(a)pyrene-7,8-diol (BP-7,8-diol) by microsomes prepared from whole skin, dermis, and epidermis of neonatal BALB/c mice pretreated with topically applied 3-methylcholanthrene (MCA) was compared. In control animals, microsomes prepared from epidermis showed higher rates of metabolism of BP and BP-7,8-diol (1.4-2.6-fold) than did microsomes prepared from whole skin or dermis. A single topical application of MCA increased the rate of metabolism of BP and BP-7,8-diol in microsomes prepared from whole skin, dermis, and epidermis. The greatest increase occurred in the epidermis. The in vivo covalent binding of [3H]BP, [3H]BP-7,8-diol, and 7,12-[3H]dimethylbenz(a)anthracene ([3H]DMBA) to DNA was found to be greater in epidermis (8.7-15.4-fold) than in whole skin or in dermis. A single topical application of MCA to BALB/c mice enhanced the in vivo binding of [3H]BP, [3H]BP-7,8-diol and [3H]DMBA to DNA of whole skin, dermis, and epidermis more than 2-fold. Exposure of Salmonella tester strains TA98 and TA100 to 2-aminoanthracene, a skin carcinogen, in the presence of an epidermal metabolic activation mixture resulted in a greater mutagenic response when compared to activation mixtures derived from whole skin or dermis. These results indicate that epidermis is the major site of polycyclic aromatic hydrocarbon metabolism and of enzyme-mediated covalent binding of polycyclic aromatic hydrocarbon carcinogens to DNA in skin of BALB/c mice and that topically applied MCA has maximum enzyme induction effects in this skin compartment.

Animals↗

PubMed1987

Benzo(e)pyrene-induced alterations in the binding of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene to DNA in Sencar mouse epidermis.

Benzo(e)pyrene [B(e)P] cotreatment slightly increases the tumor-initiating activity of benzo(a)pyrene [B(a)P] and greatly decreases the tumor-initiating activity of 7,12-dimethylbenz(a)anthracene (DMBA) in Sencar mice (DiGiovanni et al., Carcinogenesis 3: 371-375, 1982). The effects of B(e)P on the binding of B(a)P and DMBA to Sencar mouse epidermis were investigated using a protocol similar to the mouse skin tumorigenicity studies. After 12 h of exposure to 50 nmol [3H]B(a)P and low or high doses of B(e)P, the level of [3H]B(a)P bound to mouse epidermal DNA increased by 30%. However, after 24 h exposure to 50 nmol [3H]B(a)P and after 12 or 24 h of exposure to 200 nmol [3H]B(a)P, B(e)P had no effect on the amount of [3H]B(a)P bound to DNA. The ration of anti-(the isomer with the epoxide and benzylic hydroxyl on opposite faces of the molecule) B(a)P-7,8-diol-9,10-epoxide [B(a)PDE]-deoxyribonucleoside adducts to syn- (the isomer with the epoxide and benzylic hydroxyl on the same face of the molecule) B(a)PDE-deoxyribonucleoside adducts did not change at either initiating dose of B(a)P or at any time regardless of the dose of B(e)P. After 12 h of exposure to high doses of B(e)P and a 50-nmol initiating dose of B(a)P the level of [3H]B(a)P bound to DNA increased but there was no change in the proportion of particular B(a)PDE-deoxyribonucleoside adducts present. In contrast, B(e)P inhibited the binding of initiating doses of DMBA (5 and 20 nmol) to DNA after 12 and 48 h of exposure to all dose ratios of B(e)P:DMBA tested. The three major adducts, tentatively identified as anti-DMBA-3,4-diol-1,2-epoxide (DMBADE):deoxyguanosine, syn-DMBADE:deoxyadenosine and anti-DMBADE:deoxyadenosine, decreased to the same relative extent as the dose of B(e)P increased. Thus, the effects of B(e)P on the total binding of these hydrocarbons to DNA in epidermis correlate with the cocarcinogenic and anticarcinogenic effects of B(e)P on B(a)P and DMBA, respectively, in a mouse skin initiation-promotion assay. These results indicate that the mechanism of the co- or anticarcinogenic action of hydrocarbons such as B(e)P involves alteration of the binding of carcinogenic hydrocarbons to DNA. They also suggest that measurement of carcinogenic hydrocarbon-DNA adducts formed during cotreatment with other hydrocarbons will provide a rapid method for predicting the co- or anticarcinogenic effect of the other hydrocarbons.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1984

Oxidation of benzo(a)pyrene and 7,8-dihydro-7,8-dihydroxy benzo(a)pyrene by horseradish peroxidase-H2O2 intermediate: fluorometric study.

The capacity of oxidation of benzo(a)pyrene (BP) and its analog to be oxidized by peroxidases in several tissues has been studied. The kinetics of the horseradish peroxidase (HRP) oxidation of BP and 7,8-dihydro-7,8-dihydroxy benzo(a)pyrene (BP-7,8-diol) were examined. Effective ratios of H2O2 and HRP for catalytic oxidation were 13.74 for BP and 4.58 for BP-7,8-diol. The maximum ratio was approximately 90 for both hydrogen donors (BP and BP-7,8-diol) to the ES complex. The maximum ratio of oxidized BP and BP-7,8-diol to HRP was 5.7. Ks values for H2O2 were 1.68 and 6.35 microM for BP and BP-7,8-diol, respectively. The mean values of the rate constants, k5, for the oxidation of BP and BP-7,8-diol were 0.56 X 10(5) M-1 sec-1 and 4.1 X 10(5) M-1 sec-1, respectively, at low concentrations. At low concentrations a Hill plot of the oxidation of BP showed a negative value (nH = 0.5) and at high concentrations nH = 1.0. On the other hand, that of BP-7,8-diol showed positive cooperativeness (nH = 1.8). These oxidation reactions caused substrate (donor) inhibition at high concentrations. The inhibition constants, KA', were 9.8 and 5.65 microM for BP and BP-7,8-diol, respectively. The reactivity of the oxidation of BP-7,8-diol was five to six times larger than that of BP.

Benzo(a)pyrene↗

PubMed1981

[Studies on the induction by extracts from airborne particulates of benzo(a)pyrene hydroxylase and the binding of benzo(a)pyrene to DNA in the rat lung in vivo after pertracheal administration (author's transl)].

A method is described for the administration of suspended material into the rat lung. The rat is narcotized by CO2/air, the trachea is punctured and the suspension is sucked into the lung by the inhaled air (pertracheal administration, p. t. a.). BaP administered by this method is eliminated from the lung rapidly, while metabolites persist for a longer period. The radioactivity detected in the blood can be attributed predominantly to metabolites, a small fraction is unmetabolized benzo(a)pyrene. The activity of benzo(a)pyrene hydroxylase is induced in the lung after p. t. a. of extracts from airborne particulate matter. The activity increases depending on the dose until a plateau of activity is reached at high doses. Pertracheally administered BaP is bound to DNA of the lung. Pretreatment with extracts p.t.a. enhances the binding. After enzymatic digestion of DNA BaP-nucleoside adducts are detected by HPLC. According to data published in the literature to adducts are supposed to be derived from BaP-phenols and BaP-diolepoxides. It is concluded tht the components of airborne particulates can modify the activity of metabolizing enzymes and increase the rate of formation of adducts in the lung in vivo.

Animals↗

PubMed1984

Direct suppression of in vitro antibody production by mouse spleen cells by the carcinogen benzo(a)pyrene but not by the noncarcinogenic congener benzo(e)pyrene.

The role of metabolic activation of benzo(a)pyrene B(a)P in mediating its suppression of humoral immune responsiveness of the female C57BL/6 X C3H F1 (hereafter called B6C3F1) mouse was addressed in these studies. The model was the in vitro antibody response by untreated splenic suspensions, to which was added directly either B(a)P or benzo(e)pyrene B(e)P. B(a)P suppressed the antibody response to DNP-Ficoll and sheep erythrocytes but not the polyclonal antibody response to LPS. This activity neither required nor was affected by addition of a metabolic activation system (i.e., S-9 crude liver homogenate from Aroclor-induced B6C3F1 mice) at 3 times the concentration (based on determination of protein content) which readily activated cyclophosphamide. Preliminary results with radiolabeled B(a)P verified that appreciable amounts of hydroxylated metabolites of B(a)P were obtained after only a 30-min preincubation. Therefore, production of the reactive metabolites of B(a)P which mediate its carcinogenicity are not essential for its immunosuppressive activity. The results, showing a parallel in the immunosuppressive profile of activity of B(a)P and the lack of immunosuppressive activity of B(e)P following in vivo and in vitro exposure, indicate that the in vitro antibody systems offer an ideal model system to characterize the PAHs.

Animals↗