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-me Ade gly) and O-6-alkylguanine-DNA-alkyltransferase (O(6)ATase) were in vestigated in ten human cancer cell lines. Both 3-meAde gly and O(6)AT ase activities were variable among different cell lines. mRNA levels o f the O(6)ATase gene, appeared to be related to the content of O(6)ATa se 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, tallimu stine, 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 betw een the activity of O(6)ATase and 3-meAde gly in the various cell line s investigated (P<0.01), suggesting a common mechanism of regulation o f two DNA repair enzymes.