Mechanism of 2-aminopurine mutagenesis in mouse T-lymphosarcoma cells.

Molecular and Cellular Biology
I W CarasD W Martin

Abstract

We investigated the mechanism of action of 2-aminopurine (Apur) in eucaryotic cells. By analogy with studies in procaryotic systems, the base analog is presumed to incorporate into DNA predominantly opposite T where, upon subsequent DNA replication, it can mispair with C, inducing an A:T leads to G:C transition. This model predicts that Apur-induced mutagenesis will be enhanced by factors that favor formation of Apur-C mispairs, e.g., high levels of dCTP or low levels of TTP. We describe the use of a mutant T-lymphosarcoma cell line, AraC-6-1, which has an abnormally high dCTP pool and a low TTP pool, to test this prediction. AraC-6-1 cells were three- to fivefold more mutable by Apur than their parental cell line, NSU-1. This enhanced mutability by Apur could not be explained by altered incorporation of 3H-labeled Apur, by generally impaired ability to repair DNA damage, or by a direct effect of Apur on the endogenous deoxynucleotide pools. The addition of 10 microM thymidine to the growth medium of AraC-6-1 cells lowered their high dCTP pool (two- to threefold), raised the TTP pool (two- to threefold), and abolished their enhanced mutability by Apur. Further manipulation to produce an abnormally high TTP/dCTP ratio suppressed...Continue Reading

References

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Citations

Jan 1, 1987·Environmental and Molecular Mutagenesis·R RandazzoA Abbondandolo
Sep 1, 1985·Somatic Cell and Molecular Genetics·G L WeinbergD W Martin
Oct 23, 1997·Mutation Research·N N Khromov-Borisov
Jul 1, 1988·Mutation Research·B A Kunz
Aug 1, 1988·Journal of Bacteriology·R H GrafstromK Zachariasewycz

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