The metabolism and DNA binding of 3-methyl-cholanthrene

Tritiated 3-methylcholanthrene (3MC) was administered to mouse embryo cells in culture from which DNA was later isolated and hydrolysed to deoxyribonucleosides. The hydrolysate was analysed by LH20 chromatography, HPLC and fluorescence spectroscopy. The 3MC-nucleoside products were compared with the nucleoside derivatives obtained from 3MC-11,12-oxide-treated DNA and found to differ in both fluorescence spectra and chromatographic behaviour. Microsome-catalyzed DNA binding of primary metabolites of 3MC identified two metabolites for which DNA reaction was extensive. These metabolites were characterized by their chromatographic and spectrophotometric properties. The products of their microsome-induced DNA binding were isolated, and comparison with the products derived from cell-mediate 3MC-DNA reaction suggested that these metabolites might be precursors of this latter reaction. The chemical nature of the metabolites and of their DNA reaction products is discussed in relation to the "bay region" and carbonium ion concepts of the ultimate carcinogen of polycyclic hydrocarbons.