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Relationships between the Carcinogenic and Mutagenic or DNA-modifying Effects of Nitrofuran Derivatives, Including 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide, a Food Additive¹

Biochemistry Division, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo [T. Y., M. N., T. S.]; Department of Molecular Oncology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo [K. H., T. M., T. S.], Japan; and Division of Clinical Oncology, University of Wisconsin Medical School, Madison, Wisconsin 53706 [G. T. B.]

The mutagenic and DNA-modifying effects of 27 nitrofuran derivatives were studied by means of several rapid microbial assay methods. The mutagenic effects were tested with the use of Escherichia coli, B/r WP2 try^- and WP2 try^-, hcr^-; and with Salmonella typhimurium, TA1535, TA1536, TA1537, and TA1538. The DNA-modifying effects were assayed by repair tests with E. coli, rec⁺, recA13, and recB21, S. typhimurium, TA1978 (uvr⁺) and TA1538 (uvrB). Twenty-six of the 27 nitrofuran derivatives tested had mutagenic effects on E. coli, but none of them had mutagenic effects on S. typhimurium. Twenty-five compounds had DNA-modifying effects on E. coli, and 24 compounds had effects on the DNA of S. typhimurium. Fifteen of the 27 compounds are known to be carcinogenic. Fourteen of these 15 carcinogenic derivatives had mutagenic effects on E. coli and DNA-modifying effects on E. coli and S. typhimurium. Nitrofurazone gave positive results on mutagenicity and in repair tests with E. coli, but negative results on mutagenicity and in repair tests with S. typhimurium. Three derivatives reported as noncarcinogenic also showed positive mutagenic and DNA-modifying effects. One of these, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, is widely used as a food additive in Japan. The necessity for further in vivo tests on the carcinogenicities of these three compounds is indicated. The results show that several different microbial systems must be used for detection of potential carcinogens and mutagens.

¹ Supported in part by grants from the Ministry of Education, the Ministry of Health and Welfare, the Princess Takamatus Cancer Research Fund, and USPHS Research Grant CA 11946 from the National Cancer Institute.

Received 4/ 9/74. Accepted 5/ 3/74.

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