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Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation and metabolism of epoxides related to 7,12-dimethylbenz(a)anthracene.

ABSTRACT: The syntheses of 7,12-dimethylbenz[a]anthracene 5,6-oxide, 7-acetoxymethyl-12-methylbenz[a]anthracene 5,6-oxide and a product that appears to be mainly 7-hydroxymethyl-12-methylbenz[a]anthracene 5,6-oxide are described. The compounds readily rearranged to phenols in the presence of mineral acid, and 7,12-dimethylbenz[a]anthracene 5,6-oxide and its 7-hydroxymethyl derivative reacted slowly with water to yield trans-5,6-dihydro-5,6-dihydroxy-7,12-dimethylbenz[a] anthracene and trans-5,6-dihydro-5,6-dihydroxy-7-hydroxymethyl-12-methylbenz [a]anthracene respectively. Both epoxides were converted enzymically by rat liver microsomal fractions and homogenates into the related trans-dihydrodiols. The epoxides reacted chemically with GSH to form conjugates that were identical with the conjugates formed when the epoxides were incubated with rat liver homogenates. The GSH conjugates were more stable to acid than conjugates derived from other arene oxides. In the alkylation of 4-(p-nitrobenzyl)pyridine, 7,12-dimethyl-benz[a]anthracene 5,6-oxide was more active than the 5,6-oxides of 7-methylbenz[a]-anthracene and benz[a]anthracene.

SUBMITTER: Sims P

PROVIDER: S-EPMC1177481 | biostudies-other | 1973 Feb

REPOSITORIES: biostudies-other

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Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation of benz( )anthracene 8,9-oxide and 10,11-dihydrobenz( )anthracene 8,9-oxide and their metabolism by rat liver preparations.

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2013-07-22 | GSE49068 | GEO

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METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 7,12-DIMETHYLBENZ(ALPHA)ANTHRACENE BY RAT-LIVER HOMOGENATES.

Project description:1. The main products of the metabolism of 7,12-dimethylbenz[a]anthracene by rat-liver homogenates are the isomeric monohydroxymethyl derivatives. The syntheses of these compounds are described. 2. Two phenolic products and two dihydrodihydroxy compounds were formed, but none of these appeared to have been formed by hydroxylation at the ;K region'. There was little evidence for the formation of a glutathione conjugate of the hydrocarbon. 3. The monohydroxymethyl derivatives are products of the hydroxylation of the hydrocarbon in the ascorbic acid-Fe(2+)-oxygen model hydroxylating system.

| S-EPMC1206806 | biostudies-other

HepG2 treated with two Polycyclic Aromatic Hydrocarbons (benzo[a]anthracene & benzo[k]fluoranthene)

2013-07-22 | E-GEOD-49068 | biostudies-arrayexpress

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Project description:Polycyclic aromatic hydrocarbons degraders Raw sequence reads

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Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene.

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Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage.

Project description:7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1mg/kg; intraperitoneal injection) at 18weeks of age, for 14days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6 (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (?H2AX) level was determined by Western blotting. Obesity decreased (P<0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P<0.05) ?H2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P<0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P<0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced ?H2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity.

| S-EPMC4275104 | biostudies-literature

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