3-methyladenine-DNA-glycosylase and O-6-alkyl guanine-DNA-alkyltransferase activities and sensitivity to alkylating agents in human cancer cell lines

The activities and the expression of 3-methyladenine glycosylase (3-meAde gly) and O-6-alkylguanine-DNA-alkyltransferase (O(6)ATase) were investigated in ten human cancer cell lines. Both 3-meAde gly and O(6)ATase activities were variable among different cell lines. mRNA levels of the O(6)ATase gene, appeared to be related to the content of O(6)ATase in different cell lines, whereas no apparent correlation was found between mRNA of 3-meAde gly and the enzymatic activity. No correlation was found between the activity of the two enzymes and the sensitivity to alkylating agents of different structures such as CC-1065, tallimustine, dimethylsulphate (DMSO), N-methyl-N-1-nitro-N-ntirosoguanidine (MNNG), cis-diamminedichloroplatinum (cDDP) and melphalan (L-PAM). The most striking finding of this study is that a correlation exists between the activity of O(6)ATase and 3-meAde gly in the various cell lines investigated (P<0.01), suggesting a common mechanism of regulation of two DNA repair enzymes.