Aflatoxin B1-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 B1 (AFB1). Because an acute exposure may not reflect the exposure pattern of individuals whose diet may contain AFB1-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 AFB1 for three four-week periods interspersed with two four-week periods of the control diet, or (C) continuously fed 1.6 ppm of AFB1. 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 AFB1, 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 AFB1. 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 AFB1 may present a human health risk.
Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, Food and Drug Administration, Department of Health and Human Services, 3900 NCTR Road, Jefferson, AR 72079, USA. smorris@nctr.fda.gov
S M
SM
Morris
A
A
Aidoo
J J
JJ
Chen
M W
MW
Chou
D A
DA
Casciano
D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000008:administration & dosage / Q000633:toxicity*; D000821:Animal Feed; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D016296:Mutagenesis; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000187:drug effects / Q000201:enzymology
D009153:Mutagens; D016604:Aflatoxin B1; D007041:Hypoxanthine Phosphoribosyltransferase