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 microM, 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.
Zhu
W
W
Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.
Yamasaki
H
H
Mironov
N
N
D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D009153:Mutagens / Q000494:pharmacology*; D009154:Mutation; D010641:Phenotype
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D007041:Hypoxanthine Phosphoribosyltransferase