Okonogi H, Ushijima T, Zhang X B, Heddle J A, Suzuki T, Sofuni T, Felton J S, Tucker J D, Sugimura T, Nagao M
Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Carcinogenesis. 1997 Apr;18(4):745-8. doi: 10.1093/carcin/18.4.745.
The mutational spectra of carcinogenic heterocyclic amines (HCAs), 2-amino-3,4-dimethylimidazo[4,5-b]quinoline (MeIQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-9H-pyrido[2,3-b]indole (A alphaC) were studied in the colon of Big Blue mice. In 90, 115 and 105 lacI mutants from mice fed 300 p.p.m. MeIQ, 400 p.p.m. PhIP and 800 p.p.m. A alphaC, respectively, 92, 115 and 105 mutations were identified. G:C-->T:A transversions predominated with these HCAs. Mutational hot spots for base-substitution mutations caused by MeIQ, PhIP and A alphaC were in distinct sequence contexts; at 5'-GC-3', in runs of guanine and in 5'-CGT-3', respectively. Further, 30 of 115 (26%) PhIP-induced mutations were G:C base pair deletions, and eight of these deletions were in 5'-GGGA-3'. The mutational characteristics of MeIQ in the lacI gene coincided well with those in the Ha-ras gene of MeIQ-induced mouse forestomach tumors and rat Zymbal gland tumors. The characteristic single-base deletion induced by PhIP in the lacI gene also coincided well with those in the Apc gene of PhIP-induced rat colon tumors. These results suggest that the mutational characteristics of each chemical are conserved across different genes in different species.
在大蓝鼠的结肠中研究了致癌杂环胺（HCA）、2-氨基-3,4-二甲基咪唑[4,5-b]喹啉（MeIQ）、2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶（PhIP）和2-氨基-9H-吡啶并[2,3-b]吲哚（AαC）的突变谱。在分别喂食300 ppm MeIQ、400 ppm PhIP和800 ppm AαC的小鼠的90、115和105个lacI突变体中，分别鉴定出92、115和105个突变。这些HCA以G:C→T:A颠换为主。由MeIQ、PhIP和AαC引起的碱基置换突变的热点处于不同的序列背景中；分别在5'-GC-3'、鸟嘌呤重复序列和5'-CGT-3'处。此外，115个（26%）PhIP诱导的突变中有30个是G:C碱基对缺失，其中8个缺失位于5'-GGGA-3'。MeIQ在lacI基因中的突变特征与MeIQ诱导的小鼠前胃肿瘤和大鼠鼓室腺肿瘤的Ha-ras基因中的突变特征非常吻合。PhIP在lacI基因中诱导的特征性单碱基缺失也与PhIP诱导的大鼠结肠肿瘤的Apc基因中的缺失非常吻合。这些结果表明，每种化学物质的突变特征在不同物种的不同基因中是保守的。
