The study of human cells defective in repairing damaged DNA was extended, with the rationale that DNA repair-deficient cells are more susceptible to the adverse effects of carcinogens (cell killing, mutagenesis, sister chromatid exchange, and malignant transformation) than their repair-proficient counterparts. A group of 19 human tumor and eight SV40-transformed strains almost totally deficient in the repair of 0-6-methylguanine (0-6-MeG, a modified DNA base made by certain methylating agents) was identified earlier in this project. Such strains are called Mer-. Transformation by SV40, Rous sarcoma virus, adenovirus, or Epstein-Barr virus produces Mer- strains. Mer+ but not Mer- strains contain about 60,000 copies of a 22,000 MW 0-6-MeG-DNA methyltransferase (0-6-DMT) that is responsible for repairing 0-6-MeG by demethylation. Cell strains having intermediate amounts of 0-6-DMT also have intermediate sensitivity to killing by 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) or by 1-(2-chloroethyl)-1-nitrosourea (CNU) and intermediate sensitivity to the induction of sister chromatid exchanges by MNNG. Human interferons alpha and beta inactivate Mer- tumor strains, while Mer+ human tumor strains are more resistant to such treatment, indicating an association between defective repair of 0-6-MeG and sensitivity to interferons. We found 0-6-MeG to be lethal to human cells under certain conditions.
