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

Rats fed the hepatocarcinogen 2-acetylaminofluorene (2-AAF) have a low, but significantly increased, frequency of lymphocyte Hprt mutants. In this stu dy, mutants from 2-AAF-fed and control F344 rats were examined for mutation s 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-tr eated 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 transi tions. Among mutations from control rats, G:C --> A:T transition was the mo st common (43%), and there were very few G:C --> T:A transversions (5%) and no l-bp deletions. The profile of mutations from 2-AAF-fed rats was signif icantly 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 i ndicate that even weak mutational responses in the lymphocyte Hprt assay ar e capable of producing mutation profiles that reflect the DNA damage induci ng them. (C) 1999 Elsevier Science B.V. All rights reserved.