Frequency of HPRT gene mutations induced by N-methyl-N′-nitro-N-nitrosoguanidine corresponds to replication error phenotypes of cell lines

We have examined whether cells with replication error-positive (RER+) and -negative phenotype (RER-) respond differently to the mutagen MNNG, employing three RER+ and two RER- human cell lines. Cells were treated with several concentrations of MNNG, and HPRT mutants were selected phenotypically by their growth in the presence of 6-thioguanine. While the variation of the mutation frequency within each group was about an order of magnitude, it was found that MNNG induced a level of mutations in the HPRT gene some 100- to 1000-fold higher in RER+ cells than in cells with RER- phenotype. MNNG, at a concentration of 30 mu M, produced a mutation frequency 450-fold higher in HCT116 (RER+) cells than in SW480 (RER-) cells. Our findings suggest that the RER+ phenotype predisposes cells to MNNG-induced hypermutability. (C) 1998 Elsevier Science B.V.