Repair of methylated bases in mammalian cells during adaptive response to alkylating agents.
Pretreatment of H4 (rat hepatoma) cells for 48 h with non toxic doses of alkylating agents methylmethane sulfonate, (MMS), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) renders the cells more resistant to the toxic and mutagenic effects of these compounds. This adaptive response seems to reflect improved repair of methylated lesions in cellular DNA. Therefore, we measured the activity of the DNA-glycosylase for N-methylated purines (7-MeGua and 3-MeAd) and the activity of the O6-methylguanine-DNA methyltransferase in control and adapted cells. We show that the adaptive response does not significantly increase the DNA-glycosylase activity but involves the induction of methyltransferase molecules.
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D045647:DNA Glycosylases; D004260:DNA Repair; D004351:Drug Resistance; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008745:Methylation; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008780:Methyltransferases / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats
D000477:Alkylating Agents; D008769:Methylnitronitrosoguanidine; D004247:DNA; D008741:Methyl Methanesulfonate; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases