Aflatoxin B-1-induced Hprt mutations in splenic lymphocytes of Fischer 344rats. Results of an intermittent feeding trial

In a previous study, we found an increase in the mutant frequency at the Hy poxanthine phosphoribosyl transferase (Hprt) locus in the splenic lymphocyt es of Fischer 344 rats acutely exposed to aflatoxin B-1 (AFB(1)). Because a n acute exposure may not reflect the exposure pattern of individuals whose diet may contain AFB(1)-contaminated foodstuffs, we sought to determine if the feeding regimen affected the induction of Hprt mutations in the rat spl enic lymphocyte. Thus, Fischer 344 rats were fed either (A) a control diet, (B) various doses of AFB(1) for three four-week periods interspersed with two four-week periods of the control diet, or (C) continuously fed 1.6 ppm of AFB(1). Not only was a significant increase in the mutant frequency dete cted in the lymphocytes of rats fed a dose as low as 0.01 ppm of AFB(1), bu t the increase in the mutant frequency at the end of the 20-week experiment al period was consistent with an accumulation of damage induced by AFB(1). These results indicate that the rat lymphocyte/Hprt assay is useful for det ecting chronic low level exposures. Further, these data suggest that an int ermittent, low-level exposure to AFB(1) may present a human health risk. (C ) 1999 Elsevier Science B.V. All rights reserved.