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

Abstract

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.