Synthesis of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-nitrochrysene and its reaction with 2 '-deoxyguanosine-5 '-monophosphate, 2 '-deoxyadenosine-5 '-monophosphate, and calf thymus DNA in vitro

The remarkable carcinogenic activity of 6-nitrochrysene (6-NC) in several a nimal models, and its environmental presence, suggest its potential importa nce with regard to human cancer development. Depending on the bioassay mode l, 6-NC can be activated by simple nitro reduction, ring oxidation, or by a combination of ring oxidation and nitro reduction. Only the first pathway has been clearly established. Thus, this study purports to unequivocally de fine the other pathways. Toward this end, we report for the first time the synthesis of anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-6-nitrochrysen e (6-NCDE), a likely ultimate carcinogenic metabolite of 6-NC. Also, we des cribe our initial investigation of its binding with calf thymus DNA, 2'-deo xyguanosine-5'-monophosphate (2'-dGuo), and 2'-deoxyadenosine-5'-monophosph ate (2'-dAdo) in vitro. These adduct markers were then employed for compari son with those obtained in the rat after in vivo treatment with 6-NC. On th e basis of the results, it appears that the major adduct formed in the live r of rats treated with 6-NC is not derived from 6-NCDE.