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.