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© 1990 Oxford University Press

other

O6-Methylguanine (O6-MeG) and cytotoxicity: reversion analysis involving an N-methyl-N'-nitro-N-nitrosoguanidine-sensitive, O6MeG-DNA methyltransferase-deficient HeLa cell mutant

Ramaswami Kalamegham and Kaney Ebisuzaki

Cancer Research Laboratory and Department of Microbiology and Immunology, Health Sciences Center, University of Western Ontario London, Ontario, Canada N6A 5B7

In a previous communication, we proposed that N-methyl N'-nitro-N-nltrosoguanidine (MNNG)-induced cytotoxicity in an O6 (O6-MeG)-DNA methyltransfer ase-deficient (MT–) HeLa cell mutant was mainly the consequence of DNA strand breaks resulting from the failure to remove O6 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-reslstant 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.


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