Modulation of induced reversion frequency by nucleotide pool imbalance as a tool for mutant characterization

Addition of thymidine (TdR) or deoxycytidine (CdR) to the culture medium during posttreatment incubation affected the frequency of mutagen-induced reversion in three hypoxanthine-guanine phosphoribosyl transferase-deficient mutants of V79 Chinese hamster cells. With two of the mutants (E20 and I3), reversions induced by N-ethylnitrosourea, ethyl methanesulfonate, and methyl methanesulfonate were enhanced by TdR and were either decreased (E20) or not affected (I3) by CdR. With the third mutant (E21), alkylating agent-induced reversions were enhanced by CdR and decreased by TdR. Finally, 6-amino-2-hydroxypurine induced reversions were enhanced by TdR in mutant I3 and were decreased by TdR or deoxyadenosine (AdR) and enhanced by CdR in mutant E21. An attempt was made to reconcile these results with simple mutation mechanisms, based on either G:C to A:T or A:T to G:C transitions. It is suggested that the present approach may add useful information to studies of specific revertibility of mammalian cell mutants with known mutagens.