Effect of 4'-halogen substitution on the mutagenicity of trans-4-acetamidostilbene and trans-4-(N-hydroxyacetamido)stilbene in the Salmonella typhimurium test system.

The effect of halogen substituents placed at the 4' position of trans-4-acetamidostilbene (1, AAS) to alter the pattern of biotransformation and thus the mutagenicity of these derivative was evaluated by comparing the mutagenic effects of 1 on Salmonella typhimurium TA-100 with the corresponding 4'-F (2), 4'-Cl (3), and 4'-Br (4) analogues. The mutagenic properties of trans-4-(N-hydroxyacetamido)stilbene (5) and its 4'-F (6), 4'-Cl (7), and 4'-Br (8) derivatives were also evaluated in this system. Both the amides (1-4) and hydroxamic acids (5-8) required the presence of a metabolic activating system prepared from hamster liver in order to produce a mutagenic effect. All of these compounds were mutagenic to A-100. Their mutagenic potencies were markedly influenced by the 4'-halogen substituents, the relative mutagenic potencies of the amides being 2 (4'-F) greater than 1 (4'-H), 3 (4'Cl) greater than 4 (4'-Br), while the hydroxamic acids followed the order of 1 (4'-H) greater than 2 (4'-F) greater than 3 (4'-Cl), 4 (4'-Br).