The formation of 9-hydroxychrysene-1,2-diol as an intermediate in the metabolic activation of chrysene.

Abstract

9-Hydroxy-trans-1,2-dihydro-1,2-dihydroxychrysene (9-hydroxychrysene-1,2-diol), which may be the triol involved in the formation of a chrysene triol-epoxide-DNA adduct in mouse skin, was not detected when chrysene was incubated with rat-liver microsomal preparations. In separate experiments an excess of synthetic 9-hydroxychrysene-1,2-diol was added during the incubation of 3H-labelled chrysene with rat-liver microsomes and was then re-isolated. The triol was found to contain a radioactive product that had chromatographic properties identical to those of 9-hydroxychrysene-1,2-diol when examined by reverse-phase h.p.l.c., both before and after acetylation, by normal-phase h.p.l.c. and by t.l.c. both before and after oxidation. When treated with m-chloroperoxybenzoic acid, the synthetic 9-hydroxychrysene-1,2-diol formed products that possessed alkylating activity and that reacted with DNA in vitro. Examination of the triol-epoxides produced by oxidation of a mixture of synthetic and metabolic 9-hydroxychrysene-1,2-diol by t.l.c. suggested that the anti-isomer was formed.