Lack of induction of O6-methylguanine-DNA methyltransferase in mammalian cells treated with N-methyl-N'-nitro-N-nitrosoguanidine.

A synthetic DNA substrate containing O6-methyl[8-3H]-guanine was used to assay demethylation of the premutagenic base by O6-methylguanine-DNA methyltransferase in extracts of HeLa cells, Chinese hamster ovary cells and normal rat kidney cells which had been treated with multiple doses of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). No induction of methyltransferase activity was observed in any of the cell lines tested. Constitutive levels of methyltransferase in cell lines proficient (Mex+) in O6-methylguanine repair were decreased in a dose-dependent fashion by either single or multiple treatments with MNNG over a broad range of dose levels. Recovery of constitutive levels of activity required 24- to 48-h incubation periods. Repair deficient (Mex-) cell lines lacked both constitutive and inducible methyltransferase activity.