FORMATION OF GLUCURONIC ACID CONJUGATES OF 7,12-DIMETHYLBENZ(A)-ANTHRACENE PHENOLS IN 7,12-DIMETHYLBENZ(A)ANTHRACENE-TREATED HAMSTER EMBRYO CELL-CULTURES

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (10) , 3432-3437
Abstract
Secondary cultures of hamster embryo cells exposed to 0.5 nmol of the carcinogen [G-3H]7, 12-dimethylbenz(a)anthracene (DMBA) per ml medium metabolized more than 90% of the DMBA within 48 h. Samples of medium were extracted with chloroform, methanol and water. The chloroform phases contained about 1/3 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 1/2 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 material. 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.