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Mutat Res. 1998 Feb 26;398(1-2):93-9.

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

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Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, Lyon, France.


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.

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