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.
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004790:Enzyme Induction; D005260:Female; D006367:HeLa Cells / Q000201:enzymology; D006801:Humans; D007668:Kidney; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D008780:Methyltransferases / Q000235:genetics*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010053:Ovary; D051381:Rats
D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase