Modification of Mutagenicity by Fluorine-Substitution on Diazachrysene

Fluorinated derivatives of 4,10-diazachrysene (DAC) were tested for their mutagenicity in Salmonella typhimurium TA100 in the presence of rat liver S9 to investigate the metabolic activation pathway of DAC. We have previously reported that metabolism at the pyridine moiety of quinoline was related to its mutagenicity and that quinoline was deprived of its genotoxicity by fluorine-substitution at the position 3 in the pyridine moiety. DAC, an aza-analog of chrysene consisting of two quinoline moieties, has two pyridine and two benzene rings as metabolically susceptible sites in the molecule. The mutagenicity of DAC was only decreased by fluorine-substitution on both pyridine moieties. On the other hand, the mutagenicity of DAC was neither decreased by fluorine-substitution on just one pyridine moiety nor by fluorine-substitution on both benzene moieties. These results suggest that metabolic activation occurs on both pyridine moieties in DAC like in quinoline.