O6-methylguanine-DNA methyltransferase-defective human cell mutant: O6-methylguanine, DNA strand breaks and cytotoxicity.
We have isolated an isogenic O6-methylguanine (O6-MeG)-DNA methyltransferase-defective mutant from a HeLa cell line. This mutant exhibits excess DNA strand breaks and considerable cytotoxicity after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment. The increased frequency of strand breaks after MNNG treatment was not abolished by DNA synthesis inhibitors. We propose that the presence of unrepaired O6-MeG lesions leads to excess strand breaks and these, in turn, are mainly responsible for the cytotoxicity.
Kalamegham
R
R
Cancer Research Laboratory, University of Western Ontario, Canada.
Warmels-Rodenhiser
S
S
MacDonald
H
H
Ebisuzaki
K
K
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006367:HeLa Cells / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008780:Methyltransferases / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D014466:Ultraviolet Rays
D008769:Methylnitronitrosoguanidine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase