Kamiya H, Miura K, Ohtomo N, Nishimura S, Ohtsuka E
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo.
Jpn J Cancer Res. 1991 Sep;82(9):997-1002. doi: 10.1111/j.1349-7006.1991.tb01934.x.
A mutagenic DNA-adduct, O6-methylguanine, was introduced into codon 12 of the synthetic c-Ha-ras gene by cassette mutagenesis. Transfection of this modified ras gene into normal NIH3T3 cells by the calcium phosphate procedure resulted in significant induction of focus formation. The ras gene inserted into the transformed cells was found to have a G to A transition at the position of the modified base. These results indicate that an O6-methylguanine residue in DNA may lead to a mutation and be one cause of activation of the ras gene.
通过盒式诱变将一种诱变DNA加合物O6-甲基鸟嘌呤引入合成的c-Ha-ras基因的第12密码子。通过磷酸钙法将这种修饰的ras基因转染到正常的NIH3T3细胞中,导致显著诱导灶形成。发现在转化细胞中插入的ras基因在修饰碱基的位置有一个从G到A的转变。这些结果表明,DNA中的O6-甲基鸟嘌呤残基可能导致突变,并且是ras基因激活的一个原因。