Canzian F, Ushijima T, Serikawa T, Wakabayashi K, Sugimura T, Nagao M
Carcinogenesis Division, National Cancer Center Research Institute Tokyo, Japan.
Cancer Res. 1994 Dec 15;54(24):6315-7.
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-amino-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/mircrosatellite 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.
通过对85个微卫星序列长度的研究，检测了杂环胺诱导的大鼠结肠肿瘤中的微卫星不稳定性，这些序列覆盖了肿瘤和正常组织中的大部分大鼠染色体。由2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶诱导的8个结肠肿瘤中有7个至少在一个微卫星序列位点出现改变，而由2-氨基-3-甲基咪唑并[4,5-f]喹啉诱导的结肠肿瘤中未观察到突变。3个由2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶诱导的结肠肿瘤在多个微卫星中有突变，其突变率分别为85个等位基因/微卫星序列中的2个、2个和3个。这些数据表明，由2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶而非2-氨基-3-甲基咪唑并[4,5-f]喹啉诱导的大鼠结肠腺癌表现出微卫星不稳定性特征。这是在致癌作用实验动物模型中对微卫星不稳定性的首次系统研究。
