Lack of induction of o-methylguanine-dna methyltransferase in mammalian cells treated with n-methyl-n' -nitro-n-nitrosoguanidine

A synthetic DNA substrate containing O⁶-methyI(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.