Studies on the Formation of Hydrocarbon-Deoxyribonucleoside Products by the Binding of Derivatives of 7-Methylbenz[a]anthracene to DNA in Aqueous Solution and in Mouse Embryo Cells in Culture¹ Free

DNA was isolated from mouse embryo cell cultures that had been treated with 7-methylbenz[a]anthracene-³H and subsequently degraded with enzymes to deoxyribonucleosides that were chromatographed on a Sephadex LH-20 column. The resultant hydrocarbon-deoxyribonucleoside products were not present in similar enzyme digests of DNA that had been reacted in aqueous solution with either 7-bromomethylbenz[a]anthracene or 7-methylbenz[a]anthracene 5,6-oxide (the K-region epoxide). Thus, neither of these reactive derivatives is an adequate model for the 7-methylbenz[a]anthracene metabolite(s) involved in the binding of this carcinogen to DNA in cellular systems. Similarly, these hydrocarbon-deoxyribonucleoside products were not present in enzyme digests of DNA from cells treated in culture with 7-hydroxymethylbenz[a]anthracene, 5-hydroxy-7-methylbenz[a]-anthracene, cis-5,6-dihydro-5,6-dihydroxy-7-methylbenz[a]anthracene, or 7-methylbenz[a]anthracene 5,6-oxide.

These data do not support mechanisms of binding of 7-methylbenz[a]anthracene to DNA in cells that require metabolic activation of the methyl group or the formation of a K-region epoxide.