O6-methylguanine (O6-MeG) and cytotoxicity: reversion analysis involving an N-methyl-N'-nitro-N-nitrosoguanidine-sensitive, O6-MeG-DNA methyltransferase-deficient HeLa cell mutant.
In a previous communication, we proposed that N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced cytotoxicity in an O6-methylguanine (O6-MeG)-DNA methyltransferase-deficient (MT-) HeLa cell mutant was mainly the consequence of DNA strand breaks resulting from the failure to remove O6-MeG lesions. If MNNG-induced cytotoxicity, DNA strand breaks and O6-MeG lesions are related, there should be a corresponding relationship of these properties in MNNG-resistant clones derived from the MT- strain. A study of such revertants indicated that they were a heterogeneous group with increased repair of DNA strand breaks and O6-MeG lesions and increased resistance to the cytotoxic effects of MNNG. These observations support the hypothesis relating O6-MeG, DNA strand breaks and cytotoxicity. The relationship of these 'revertants' to the MT- and wild-type strains is discussed.
Kalamegham
R
R
Cancer Research Laboratory, University of Western Ontario, London, Canada.
Ebisuzaki
K
K
D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D004249:DNA Damage; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000633:toxicity; D006367:HeLa Cells / Q000201:enzymology*; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D008780:Methyltransferases / Q000378:metabolism*; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D011687:Purines / Q000378:metabolism
D011687:Purines; D008769:Methylnitronitrosoguanidine; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase