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Among various types of drugs designed for use in cancer chemotherapy, some have the potential for alkylation. After metabolic activation, these chemicals attack DNA and alkylate their bases, thereby preventing multiplication of rapidly growing tumor cells. Some of alkylated bases cause mutations, leading to untoward induction of tumors. To search for the rationale to separate lethal and mutagenic...
To examine involvement of mismatch repair system in alkylation-induced apoptosis and mutagenesis, cell lines defective in the Mgmt gene encoding a DNA repair enzyme, O 6 -methylguanine-DNA methyltransferase, and/or the Mlh1 gene encoding a protein involved in mismatch repair were established from gene-targeted mice. Mgmt -/- cells are hypersensitive to the killing effect...
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