3-methyladenine-DNA-glycosylase and O6-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 O6-alkylguanine-DNA-alkyltransferase (O6 ATase) were investigated in ten human cancer cell lines. Both 3-meAde gly and O6 ATase activities were variable among different cell lines. mRNA levels of the O6 ATase gene, appeared to be related to the content of O6 ATase in different cell lines, whereas no apparent correlation was found between mRNA of 3-meAde gly and the enzyme 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'-nitro-N-nitrosoguanidine (MNNG), cis-diamminedichloroplatinum (cDDP) and melphalan (L-PAM). The most striking finding of this study is that a correlation exists between the activity of O6 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.
Damia
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Imperatori
L
L
Citti
L
L
Mariani
L
L
D'Incalci
M
M
D000477:Alkylating Agents / Q000494:pharmacology* / Q000633:toxicity; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics* / Q000633:toxicity; D002273:Carcinogens / Q000494:pharmacology* / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity; D045647:DNA Glycosylases; D004214:Distamycins / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D008558:Melphalan / Q000494:pharmacology / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology / Q000633:toxicity; D008780:Methyltransferases / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology / Q000633:toxicity; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity; D013463:Sulfuric Acid Esters / Q000494:pharmacology / Q000633:toxicity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000477:Alkylating Agents; D018906:Antineoplastic Agents, Alkylating; D002273:Carcinogens; D004214:Distamycins; D009588:Nitrogen Mustard Compounds; D012333:RNA, Messenger; D013463:Sulfuric Acid Esters; D008769:Methylnitronitrosoguanidine; C066900:tallimustine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; C007482:dimethyl sulfate; D002945:Cisplatin; D008558:Melphalan