Mutagenic Effect of 7,12-Dimethylbenz[a]anthracene-epidioxide on Salmonella typhimurium

Abstract

7,12-Dimethylbenz[a]anthracene-7,12-epidioxide (DMBAO₂) generated in situ by light-sensitized oxygenation of 7,12-dimethylbenz[a]anthracene (DMBA) is strongly mutagenic to Salmonella typhimurium. DMBAO₂ generated by rat liver microsomes is only moderately mutagenic. Mutagenicity cannot be shown when DMBAO₂ is added directly to the medium. Earlier findings indicated that DMBAO₂ is a major metabolite of DMBA by liver cytochrome P-450 oxygenase. Light-sensitized oxygenation of DMBA results in the same product in near quantitative yield with no other detectable product. We thus conclude that DMBAO₂ is a mutagen that cannot enter a cell or reach the genetic apparatus before destruction. It can exhibit its maximum effect only when DMBA is allowed to enter the cell first before oxygenation to DMBAO₂. These results also lead to the identification of a photoactivated product.