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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

✍ Scribed by Minoru Toyota; Toshikazu Ushijima; John H. Weisburger; Yoko Hosoya; Federico Canzian; Abraham Rivenson; Kohzoh Imai; Takashi Sugimura; Minako Nagao

Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
596 KB
Volume
15
Category
Article
ISSN
0899-1987

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✦ Synopsis

Microsatellite instability (MI) and loss of heterozygosity (LOH)

were examined in mammary tumors induced in Sprague-Dawley x F344 F1 female rats by 2-amino-l-methyl-6-phenylimidazo[4,5-blpyridine (PhlP). Examination of 62 microsatellite loci revealed M I in nine of 15 (60%) PhlP-induced mammary tumors, and five of these MI-positive tumors had mutations in more than one microsatellite locus. In contrast, two of 12 (17%) 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors were MI positive but had mutations at only one locus each. Further, by using 37 polymorphic markers specific LOH was observed in four of 15 PhlPinduced mammary tumors on distal parts of rat chromosome 10, which is homologous to human chromosome 17q. with no background level of LOH. Similarly, DMBA-induced mammary tumors showed specific LOH on the same region of chromosome 10. These data suggest that mismatch-repair deficiency and loss of chromosome 10 are involved in carcinogenesis of PhlP-induced rat mammary tumors.

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