Sequence specificity of Hprt lymphocyte mutation in rats fed the hepatocarcinogen 2-acetylaminofluorene

Abstract

Rats fed the hepatocarcinogen 2-acetylaminofluorene (2-AAF) have a low, but significantly increased, frequency of lymphocyte Hprt mutants. In this study, mutants from 2-AAF-fed and control F344 rats were examined for mutations in the Hprt gene in order to determine if the 2-AAF treatment resulted in an agent-specific mutation profile. The most common mutation from 2-AAF-treated rats was G:C→T:A transversion (32% of all mutations) followed by 1-basepair (bp) deletion (19%); there were very few (5%) G:C→A:T transitions. Among mutations from control rats, G:C→A:T transition was the most common (43%), and there were very few G:C→T:A transversions (5%) and no 1-bp deletions. The profile of mutations from 2-AAF-fed rats was significantly different from control rats ( P=0.003) and was consistent with the types of mutations produced by 2-AAF in vitro. The results of this study indicate that even weak mutational responses in the lymphocyte Hprt assay are capable of producing mutation profiles that reflect the DNA damage inducing them.