DNA binding and mutagenicity of 7-substituted derivatives of benz[A]anthracene

The binding of carcinogenic 7-hydroxymethylbenz[a]anthracene (7-HOCH2-B[a]A) and 7-acetoxymethylbenz[a]anthracene (7-AcOCH2-B[a]A) to calf thymus DNA was studied in the presence or absence of microsomal enzymes or nucleoside phosphates. In the absence of microsomes or ATP little or no binding was detected for either hydrocarbon (HC). Microsomal enzymes significantly enhanced the binding of both HC's to DNA when compared to control as measured by radioactivity bound to DNA. When 7-HOCH2-B[a]A was incubated at 37 degrees with ATP there was a linear increase in binding over a six hr period. Of the nucleoside phosphates tested, ATP, and to a lesser extent ADP and CTP, mediated binding of 7-HOCH2-B[a]A suggesting formation of a reactive phosphate ester. Mutagenicity studies with 7-acetoxymethyl, 7-hydroxymethyl, 7-formyl-, 7-methyl-, and 7-methoxymethyl-B[a]A were conducted using the Salmonella reverse mutation assay. All compounds exhibited mutagenic activity in the presence of S-9; only 7-AcOCH2-B[a]A was active without S-9 indicating this compound to be an ultimate mutagen.