MUTAGENICITY OF THE BAY-REGION DIOL-EPOXIDES AND OTHER BENZO-RING DERIVATIVES OF DIBENZO(A,H)PYRENE AND DIBENZO(A,I)PYRENE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (7) , 2589-2597
Abstract
The mutagenic activities of dibenzo(a,h)pyrene, dibenzo(a,i)pyrene and 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-dihydrobenzo(a,i)pyrene are the expected dihydrodiol precursors of bay-region diol-epoxides; they were metabolized by a cytochrome P-450-dependent monooxygenase system 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; this suggests 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 1.5-5 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.

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