Kito K, Kihana T, Sugita A, Murao S, Akehi S, Sato M, Tachibana M, Kimura S, Ueda N
First Department of Pathology, Ehime University School of Medicine, Japan.
Mol Carcinog. 1996 Oct;17(2):78-83. doi: 10.1002/(SICI)1098-2744(199610)17:2<78::AID-MC4>3.0.CO;2-P.
To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (AGC-->GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors.
为了确定在人类乳腺癌中常见的p53改变在大鼠乳腺肿瘤中是否也普遍存在，我们检测了24只经7,12-二甲基苯并[a]蒽（DMBA）处理的大鼠的40个肿瘤以及14只经N-亚硝基-N-甲基脲（NMU，一种N-亚硝基化合物）处理的大鼠的34个肿瘤。DMBA和NMU是已知的遗传毒性诱变剂。通过聚合酶链反应单链构象多态性分析和直接测序检测p53和Ha-ras基因的整个编码区是否存在突变。40个DMBA诱导的乳腺肿瘤中有1个发生了p53突变，即密码子307处的单碱基替换（AGC→GGC），导致氨基酸从Ser变为Gly。在NMU诱导的肿瘤中未发现突变。NMU组密码子12处的Ha-ras基因突变发生率为79%（34个中有27个），DMBA组密码子61处的发生率为23%（40个中有9个）。因此，与Ha-ras突变不同，p53突变似乎不是化学诱导的大鼠乳腺肿瘤致癌的先决条件。
