Adaptive resynthesis of O super(6)-methylguanine-accepting protein can explain the differences between mammalian cells proficient and deficient in methyl excision repair

Mammalian cells have been classified as proficient (Mer super(+)) or deficient (Mer super(-)) in methyl excision repair in terms of their cytotoxic reactions to agents that form O super(6)-alkylguanine and their abilities to reactivate alkylated adeoviruses. O super(6)-Methylguanine (O super(6) MeGua) is considered to be a lethal, mutagenic, and carcinogenic lesion. The authors measured the abilities of cell extracts to transfer the methyl group from an exogenous DNA containing O super(6)MeGua to acceptor protein. The constitutive level of acceptor activity was independent of the Mer phenotype. Treatment of cells with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) results in a dose-dependent decrease in the acceptor activity in extracts because the rapid reaction between endogenous O super(6)MeGua and acceptor protein makes the latter unavailable for further reaction. However, Mer super(+) cells, which are resistant to MNNG, rapidly resynthesize new acceptor protein, and the activity returns to the basal level in approximately equals 90 min. In Mer super(-) tumor cells and Chinese hamster cells, which are sensitive to MNNG, resynthesis is not detectable in 90 min.