Kakiuchi H, Ushijima T, Ochiai M, Imai K, Ito N, Yachi A, Sugimura T, Nagao M
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Mol Carcinog. 1993;8(1):44-8. doi: 10.1002/mc.2940080110.
Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymerase chain reaction--direct sequencing in seven colon tumors in F344 rats induced by 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1), 11 induced by 2-amino-3-methylimidazo[4,5-f]quinoline, and nine induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. A Ki-ras gene mutation (G-->T at the second position in codon 12) was found in one Glu-P-1-induced colon adenocarcinoma. None of the other 26 tumors had mutations in any of these three ras family genes. These results indicate that in rats, colon carcinogenesis induced by heterocyclic amines may be induced by alterations of other oncogenes or tumor suppressor genes. We think this experimental system using carcinogens to which humans are exposed is a good model for studying alterations of other genes in human colon tumors in which no Ki-ras alterations are observed.
已知熟食中存在的杂环胺会在F344大鼠中高发病率地诱发结肠肿瘤，这表明大鼠结肠癌变过程中可能像人类一样存在ras基因激活现象。我们通过聚合酶链反应-直接测序法，检测了由2-氨基-6-甲基二吡啶并[1,2-a:3',2'-d]咪唑（Glu-P-1）诱发的7例F344大鼠结肠肿瘤、由2-氨基-3-甲基咪唑[4,5-f]喹啉诱发的11例肿瘤以及由2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶诱发的9例肿瘤中Ki-ras、Ha-ras和N-ras基因第12、13和61密码子的突变情况。在1例Glu-P-1诱发的结肠腺癌中发现了Ki-ras基因突变（密码子12第二位的G→T）。其他26例肿瘤在这三个ras家族基因中均未发生突变。这些结果表明，在大鼠中，杂环胺诱发的结肠癌变可能是由其他致癌基因或抑癌基因的改变所引起。我们认为，这个使用人类接触的致癌物的实验系统，是研究未观察到Ki-ras改变的人类结肠肿瘤中其他基因改变的良好模型。
