Formation of glucuronic acid conjugates of 7,12-dimethylbenz(a)anthracene phenols in 7,12-dimethylbenz(a)anthracene-treated hamster embryo cell cultures.
Secondary cultures of hamster embryo cells exposed to 0.5 nmol [G-3H]7,12-dimethylbenz(a)anthracene (DMBA) per ml medium metabolized more than 90% of the DMBA within 48 hr. Samples of medium were extracted with chloroform, methanol, and water. The chloroform phases contained about one-third of the DMBA metabolites; the major chloroform-extractable metabolite was 8,9-dihydro-8,9-dihydroxy-7,12-dimethylbenz(a)anthracene. Beta-glucuronidase treatment of the aqueous methanol-soluble metabolites converted almost one-half of them to chloroform-soluble metabolites, of which more than 80% were identified as phenolic derivatives of DMBA. Similar metabolite profiles were obtained by treating the medium with beta-glucuronidase before chloroform extraction. Separation of the methyl group-hydroxylated derivatives of DMBA from the phenolic derivatives was accomplished by high-pressure liquid chromatography. Small amounts of hydroxymethyl derivatives were detected only in the chloroform-extractable material, whereas DMBA phenols were the major component of the beta-glucuronidase-released mateirla. These results indicate that the major pathway of DMBA metabolism in hamster embryo cells is oxidation of the aromatic rings and not oxidation of the methyl groups.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism*; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D002725:Chloroform; D005965:Glucuronates / Q000378:metabolism*; D005966:Glucuronidase / Q000494:pharmacology; D010636:Phenols / Q000378:metabolism*; D012995:Solubility
D001551:Benz(a)Anthracenes; D005965:Glucuronates; D010636:Phenols; D015127:9,10-Dimethyl-1,2-benzanthracene; D002725:Chloroform; D005966:Glucuronidase