The effects of a number of 4-nitroquinoline 1-oxide and 4-nitropyridine I-oxide derivatives, with varying carcino genic potencies, on the scission of proteins linking DNA

The effects of a number of 4-nitroquinoline 1-oxide and 4-nitropyridine I-oxide derivatives, with varying carcino genic potencies, on the scission of proteins linking DNA were studied in cultured mouse fibroblasts, strain L . P3. With twenty-two 4-nitroquinoline I-oxide derivatives and twelve 4-nitropyridine 1-oxide derivatives tested, an excel lent correlation was found between the scission effect of each compound and its carcinogenicity. All carcinogens, whether strong or weak, showed positive results in the scission test. Strong carcinogens such as 4-nitroquinoline 1-oxide, 2-methyl-4-nitroquinoline 1-oxide, 6-methyl-4nitroquinoline 1-oxide, 6-chloro-4-nitroquinoline 1-oxide, and 4-hydroxyaminoquinoline 1-oxide induced the scission at a low concentration of 1 x 10 M, while weak carcinogens such as 3-methyl-4-nitroquinoline 1-oxide, 6-nbutyl-4-nitroquinoline 1-oxide, 6-tert-butyl-4-nitroquinoline 1-oxide, 6-n-hexyl-4-nitroquinoline 1-oxide, and 6-car boxy-4-nitroquinoline 1-oxide only produced the same effect at dose levels higher than S x l0@ M. On the other hand, some noncarcinogenic derivatives such as 8-nitroquinoline 1-oxide, 4-hydroxy-quinoline 1-oxide, 4-aminoquinoline 1oxide, and 6-nitroquinoline could not induce the scission, while other noncarcinogens such as 3-nitroquinoline 1oxide, 5-nitroquinoline 1-oxide, and 5-nitroquinoline did induce scission at concentrations higher than 1 x 10@ M. Throughout these tests the effective concentrations of active compounds were generally much lower than the concentra tion at which the compounds were cytotoxic. The implication of the results and the feasibility of the present method of analysis as a screening procedure for potential carcinogens and mutagens are discussed.