A quantitative comparison of the mutagenicity of carcinogenic polycyclic hydrocarbon derivatives in cultured mammalian cells

Abstract

The mutagenicity of a series of reactive polycyclic hydrocarbon derivatives has been studied using Chinese hamster (V79) cells in culture and, as a mutational marker, resistance to the purine analogue 8‐azaguanine. The compounds were compared by relating mutation frequency to the dose applied (mutagenic effectiveness) to induced cytotoxicity (mutagenic efficiency) and to the extent of reaction of the hydrocarbon with DNA (absolute mutagenic efficiency). In each case anti‐benzo(a)pyrene (BP)—7,8 dihydrodiol‐9,10 oxide, the suspected ultimate carcinogenic form of benzo(a)pyrene, was by far the most potent of the compounds tested. Furthermore, the mutagenicity of the syn‐ and anti‐BP‐diolepoxide isomers correlated positively with their documented carcinogenic potency. Differences in mutagenic effectiveness are ascribed to predicted differences in the ability of each derivative to form a carbonium ion. Variations in mutagenic efficiency and absolute mutagenic efficiency were more difficult to explain. The latter findings are discussed in relation to the types of hydrocarbon‐DNA product obtained with each compound and also to the possibility of a variable cellular response to more subtle differences in the chemistry of the hydrocarbon‐DNA interaction.