Ushijima T, Kakiuchi H, Makino H, Hasegawa R, Ishizaka Y, Hirai H, Yazaki Y, Ito N, Sugimura T, Nagao M
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Mol Carcinog. 1994 May;10(1):38-44. doi: 10.1002/mc.2940100107.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant of the heterocyclic amines, a group of potent carcinogens contained in cooked meat and fish. Female F344 rats fed a diet containing 100 or 400 ppm PhIP developed mammary carcinomas within 104 or 52 wk, respectively, at the rate of 47% for each group; these carcinomas were examined for mutations in three members of the ras gene family and in the p53 gene. Single-strand conformation polymorphism (SSCP) analysis and direct sequencing demonstrated a G-->A transition at the second position of Ha-ras codon 12, with the resultant substitution of glutamic acid for glycine, in two of 10 carcinomas induced by 100 ppm PhIP and in one of seven induced by the 400 ppm dose. No mutations in Ki-ras or N-ras were detected. cDNA polymerase chain reaction-SSCP analysis and direct sequencing demonstrated a G-->T transversion at the third position of p53 codon 130, with the resultant substitution of asparagine for lysine, in one of the 10 carcinomas induced by 100 ppm of PhIP for which freshly frozen samples were available. PhIP-induced rat mammary carcinogenesis can be regarded as a unique system in that rat mammary carcinomas are negative for ras and p53 mutations.
2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶（PhIP）是杂环胺中含量最为丰富的一种，杂环胺是一类存在于熟肉和鱼肉中的强效致癌物。给雌性F344大鼠喂食含100 ppm或400 ppm PhIP的日粮，分别在104周或52周内诱发了乳腺癌，每组诱发率均为47%；对这些乳腺癌进行了ras基因家族三个成员和p53基因的突变检测。单链构象多态性（SSCP）分析和直接测序显示，在由100 ppm PhIP诱发的10例癌中的2例以及由400 ppm剂量诱发的7例癌中的1例中，Ha-ras密码子12的第二位发生了G→A转换，导致甘氨酸被谷氨酸取代。未检测到Ki-ras或N-ras的突变。cDNA聚合酶链反应-SSCP分析和直接测序显示，在有新鲜冷冻样本的由100 ppm PhIP诱发的10例癌中的1例中，p53密码子130的第三位发生了G→T颠换，导致赖氨酸被天冬酰胺取代。PhIP诱发的大鼠乳腺癌发生可被视为一个独特的系统，因为大鼠乳腺癌的ras和p53突变呈阴性。
