MICROSATELLITE INSTABILITY AND LOSS OF HETEROZYGOSITY ON CHROMOSOME-10 IN RAT MAMMARY-TUMORS INDUCED BY 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE

Microsatellite instability (MI) and loss of heterozygosity (LOH) were examined in mammary tumors induced in Sprague-Dawley x F344 F-1 female rats by 2-amino-1-methyl-6-phenylimidato[4,5-b]pyridine (PhIP). Exami nation of 62 microsatellite loci revealed MI in nine of 15 (60%) PhIP- induced mammary tumors, and five of these MI-positive tumors had mutat ions in more than one microsatellite locus. In contrast, two of 12 (17 %) 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were M I positive but had mutations at only one locus each. Further, by using 37 polymorphic markers specific LOH was observed in four of 15 PhIP-i nduced mammary tumors on distal parts of rat chromosome 10, which is h omologous to human chromosome 17q, with no background level of LOH. Si milarly, DMBA-induced mammary tumors showed specific LOH on the same r egion of chromosome 10. These data suggest that mismatch-repair defici ency and loss of chromosome 10 are involved in carcinogenesis of PhIP- induced rat mammary tumors. (C) 1996 Wiley-Liss, Inc.