Massey T E, Devereux T R, Maronpot R R, Foley J F, Anderson M W
Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Carcinogenesis. 1995 May;16(5):1065-9. doi: 10.1093/carcin/16.5.1065.
The murine K-ras proto-oncogene is hypothesized to be a pulmonary adenoma susceptibility gene. This postulate is supported by the previous demonstration of a preference for mutation of the K-ras allele from the susceptible parent in lung tumors of A/J x C3H F1 mice. We have examined K-ras activation in control and vinyl carbamate (VC) (single dose 0.03 mumol/g i.p.) treated B6CF1 mice, the progeny of resistant C57BL/6J and intermediately sensitive BALB/cJ parents. Thirty-four of 37 tumors from VC-treated mice and 17 of 23 from controls contained activating K-ras mutations. The spectra of mutations in codons 12 and 61 of K-ras were similar for the two groups, except that 7 tumors from VC-treated mice had A-->T transversions in the second base of codon 61; none were observed in tumors from saline-treated animals. PCR-based genotyping of first exon K-ras mutations revealed that the vast majority (15 of 18) of the mutations were in the BALB/cJ allele. Furthermore, the three tumors with mutated C57BL/6J K-ras were among the smallest tumors analyzed. These results are consistent with previous findings in other mouse hybrids showing parental bias for K-ras mutations and suggest that mutation of the allele of the susceptible parent may provide a growth advantage to the tumor.
鼠源K-ras原癌基因被推测为肺腺瘤易感基因。这一假设得到了之前研究结果的支持，即在A/J×C3H F1小鼠的肺肿瘤中，K-ras等位基因更倾向于发生来自易感亲本的突变。我们检测了对照小鼠和经氨基甲酸乙烯酯（VC）（腹腔注射单剂量0.03 μmol/g）处理的B6CF1小鼠（抗性C57BL/6J和中度敏感BALB/cJ亲本的后代）中K-ras的激活情况。经VC处理的小鼠的37个肿瘤中有34个以及对照小鼠的23个肿瘤中有17个含有激活的K-ras突变。两组中K-ras密码子12和61的突变谱相似，不过经VC处理的小鼠的7个肿瘤在密码子61的第二个碱基处发生了A→T颠换；在生理盐水处理的动物的肿瘤中未观察到这种情况。基于PCR的K-ras基因第一外显子突变基因分型显示，绝大多数（18个中的15个）突变发生在BALB/cJ等位基因中。此外，三个发生C57BL/6J K-ras突变的肿瘤是所分析的最小的肿瘤。这些结果与之前在其他小鼠杂交种中的发现一致，表明易感亲本等位基因的突变可能为肿瘤提供生长优势。
