Aflatoxin B-1-Induced Hprt Mutations In Splenic Lymphocytes Of Fischer 344 Rats. Results Of An Intermittent Feeding Trial

In a previous study, we found an increase in the mutant frequency at the Hypoxanthine phosphoribosyl transferase (Hprt) locus in the splenic lymphocytes of Fischer 344 rats acutely exposed to aflatoxin B-1 (AFB(1)). Because an 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 splenic 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 detected in the lymphocytes of rats fed a dose as low as 0.01 ppm of AFB(1), but the increase in the mutant frequency at the end of the 20-week experimental period was consistent with an accumulation of damage induced by AFB(1). These results indicate that the rat lymphocyte/Hprt assay is useful for detecting chronic low level exposures. Further, these data suggest that an intermittent, low-level exposure to AFB(1) may present a human health risk. (C) 1999 Elsevier Science B.V. All rights reserved.