Baron H M, Bobrisheva I V, Varshaver N B
Laboratory of Somatic Cell Genetics, Russian Academy of Sciences, Moscow.
Cancer Genet Cytogenet. 1992 Aug;62(1):15-20. doi: 10.1016/0165-4608(92)90030-c.
The induction of gene mutations and chromosome aberrations by plasmid pEJ6.6 carrying the activated c-Ha-ras-1 oncogene from human bladder carcinoma was studied in cultured Chinese hamster cells. Both an increase in the frequency of hypoxanthine-phosphoribosyltransferase-deficient (HPRT-) mutants and chromosome aberrations was observed after pEJ6.6 transfection as compared to control series (pBR322). In order to define whether it is the oncogene which is responsible for the mutagenic effect of pEJ6.6, a derivative of c-Ha-ras-1 carrying a deletion in its coding region was constructed. As shown in all experiments, the frequency of HPRT- mutants after treatment with pEJ6.6 plasmid exceeded that in control dishes treated by pEJ6.6 plasmid with an inactivated oncogene. The effect was rather weak but statistically significant. Thus, the results of experiments carried out show that the mutagenic activity of pEJ6.6 plasmid is chiefly determined by its oncogene. The role of the mutagenic effects of activated oncogenes in malignant transformation is discussed.
研究了携带源自人膀胱癌的活化型c-Ha-ras-1癌基因的质粒pEJ6.6在培养的中国仓鼠细胞中诱导基因突变和染色体畸变的情况。与对照系列（pBR322）相比，pEJ6.6转染后观察到次黄嘌呤-磷酸核糖基转移酶缺陷（HPRT-）突变体频率和染色体畸变均增加。为了确定是否是癌基因导致了pEJ6.6的诱变作用，构建了一种在其编码区带有缺失的c-Ha-ras-1衍生物。如所有实验所示，用pEJ6.6质粒处理后的HPRT-突变体频率超过了用无活性癌基因的pEJ6.6质粒处理的对照培养皿中的频率。该效应相当微弱但具有统计学意义。因此，所进行的实验结果表明，pEJ6.6质粒的诱变活性主要由其癌基因决定。讨论了活化癌基因的诱变作用在恶性转化中的作用。
