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Instability of Microsatellites in Rat Colon Tumors Induced by Heterocyclic Amines¹

Carcinogenesis Division, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104 [F. C., T. U., K. W., T. Su., M. N.], and Institute of Laboratory Animals, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-01 [T. Se.], Japan

Microsatellite instability in rat colon tumors induced by heterocyclic amines was examined by studies on the lengths of 85 microsatellite sequences, covering most of the rat chromosomes in tumors and normal tissues. Seven of eight colon tumors induced by 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine showed alterations at least at one locus of microsatellite sequences, whereas no mutations were observed in colon tumors induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Three 2-a-mino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced colon tumors had mutations in more than one microsatellite, their mutation rates being 2 of 85, 2 of 85, and 3 of 85 allele/microsatellite sequence, respectively. These data suggest that rat colon adenocarcinomas induced by 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine but not 2-amino-3-methylimidazo[4,5-f]quinoline show a trait of microsatellite instability. This is the first systematic study of microsatellite instability in experimental animal models of carcinogenesis.

¹ This work is supported by a Grant-in-Aid for a comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare and a Grant-in-Aid for Cancer Research from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed.

Received 10/11/94. Accepted 11/ 1/94.

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