SELECTIVE ACTIVATION OF SOME DIHYDRODIOLS OF SEVERAL POLYCYCLIC AROMATIC-HYDROCARBONS TO MUTAGENIC PRODUCTS BY PROSTAGLANDIN SYNTHETASE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 1620-1623
Abstract
The ability of prostaglandin synthetase (PGS) to cooxidize benzo(a)pyrene, benzo(a)anthracene, chrysene and several of their dihydrodiol derivatives to mutagenic products was tested with Salmonella typhimurium strains TA98 and TA100. The microsomal fraction of ram seminal vesicles, a known source of PGS, in the presence of the PGS substrate arachidonic acid, metabolized benzo(a)pyrene-7,8-dihydrodiol, benzo(a)anthracene-3,4-dihydrodiol and chrysene-1,2-dihydrodiol to mutagenic products. This activity was inhibited by the PGS inhibitor indomethacin. Unlike the PGS system, however, a cytochrome P-450-reduced NADP-dependent system, present in an Aroclor 1254-induced rat liver 9000 .times. g supernatant fraction, also activated the parent compounds [benzo(a)pyrene, benzo(a)anthracene, chrysene] and several other benzo(a)anthracene dihydrodiols (the 1,2-dihydrodiol, the 8,9-dihydrodiol and the 10,11-dihydrodiol). The chrysene trans-3,4, trans-5,6 and cis-5,6 diols were not activated to mutagens by either system. The PGS system appears to be more selective than does the cytochrome P-450 system in the activation of polycyclic aromatic hydrocarbons to mutagenic products, activating only those dihydrodiols with adjacent double bonds in the bay region from which the bay-region diol-epoxides are formed.