Expression of the truncated E. coli O6-methylguanine methyltransferase gene in repair-deficient human cells and restoration of cellular resistance to alkylating agents.
We have constructed a truncated E. coli O6-methylguanine methyltransferase (MT) gene (ada gene) to express the MT activity for O6-methylguanine and O4-methylthymine but not for methylphosphotriester in human cells and transferred it into Mer- HeLa MR cells. The transfectant cells expressed the truncated E. coli MT were resistant to alkylating agents as same as the transfectant cells with the intact ada gene in cell killing, sister-chromatid exchange induction and host-cell reactivation of adenovirus 5. These results strongly suggest that methylphosphotriester may not contribute to the biological effect of alkylating agents in human cells.
D000477:Alkylating Agents / Q000633:toxicity*; D002460:Cell Line; D003001:Cloning, Molecular; D004260:DNA Repair; D004351:Drug Resistance; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012854:Sister Chromatid Exchange
D000477:Alkylating Agents; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase