The mycotoxin fumonisin induces apoptosis in cultured human cells and in livers and kidneys of rats.
Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme, a fungus that infects corn and other grains in the U.S. Fumonisin ingestion causes a variety of effects including equine leukoencephalomalacia and porcine pulmonary edema, and has been associated epidemiologically with human esophageal cancer. Fumonisin B1 produces growth inhibition and increased apoptosis in primary human keratinocyte cultures and in HET-1A cells. In order to set the doses for a 2-year tumor bioassay, male and female F344 rats were fed fumonisin B1 (99, 163, 234, and 484 ppm) for 28 days and the organs examined histologically. There was a dose dependent decrease in liver and kidney weights in the rats. The liver weight loss was accompanied by the induction of apoptosis and hepatocellular and bile duct hyperplasia in both sexes, with the female rats being more responsive at lower doses. The induction of tubular epithelial cell apoptosis was the primary response of the kidneys to dietary fumonisin B1. Apoptosis was present at all doses in the kidneys of the male rats, and occurred in the females only at 163, 234, and 484 ppm fumonisin B1. These results demonstrate that fumonisin B1 treatment causes a similar increase in apoptosis both in vivo and in vitro.
Tolleson
W H
WH
National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Dooley
K L
KL
Sheldon
W G
WG
Thurman
J D
JD
Bucci
T J
TJ
Howard
P C
PC
D000818:Animals; D017209:Apoptosis; D002274:Carcinogens, Environmental / Q000494:pharmacology*; D002455:Cell Division; D002461:Cell Line, Transformed; D004848:Epithelium; D004947:Esophagus; D005260:Female; D037341:Fumonisins; D006801:Humans; D007668:Kidney / Q000166:cytology*; D008099:Liver / Q000166:cytology*; D008297:Male; D009183:Mycotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D002274:Carcinogens, Environmental; D037341:Fumonisins; D009183:Mycotoxins; C056933:fumonisin B1