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^-HeLle MR cells. The transfectant cells expressed the truncated O⁶-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. The results strongly suggest that methylphosphotriester may not contribute to the biological effect of alkylating agents in human cells.