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Breakage of a DNA-Protein Complex Induced by 4-Nitroquinoline 1-Oxide, 4-Nitropyridine 1-Oxide, and Their Derivatives in Cultured Mouse Fibroblasts

Department of Virology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108 [T. A., T. I., M. S.]; and Chemotherapy Division, National Cancer Center Research Institute, Tsukiji 5-chome, Chuo-ku, Tokyo 104 [Y. K.], Japan

The effects of a number of 4-nitroquinoline 1-oxide and 4-nitropyridine 1-oxide derivatives, with varying carcinogenic potencies, on the scission of proteins linking DNA were studied in cultured mouse fibroblasts, strain L·P3. With twenty-two 4-nitroquinoline 1-oxide derivatives and twelve 4-nitropyridine 1-oxide derivatives tested, an excellent 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-4-nitroquinoline 1-oxide, 6-chloro-4-nitroquinoline 1-oxide, and 4-hydroxyaminoquinoline 1-oxide induced the scission at a low concentration of 1 x 10^-5 M, while weak carcinogens such as 3-methyl-4-nitroquinoline 1-oxide, 6-n-butyl-4-nitroquinoline 1-oxide, 6-tert-butyl-4-nitroquinoline 1-oxide, 6-n-hexyl-4-nitroquinoline 1-oxide, and 6-carboxy-4-nitroquinoline 1-oxide only produced the same effect at dose levels higher than 5 x 10^-5 M. On the other hand, some noncarcinogenic derivatives such as 8-nitroquinoline 1-oxide, 4-hydroxy-quinoline 1-oxide, 4-aminoquinoline 1-oxide, and 6-nitroquinoline could not induce the scission, while other noncarcinogens such as 3-nitroquinoline 1-oxide, 5-nitroquinoline l-oxide, and 5-nitroquinoline did induce scission at concentrations higher than 1 x 10^-4 M. Throughout these tests the effective concentrations of active compounds were generally much lower than the concentration 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.

Received 1/ 2/74. Accepted 10/ 8/74.