IN-VIVO EFFECTS OF FUMONISIN-B-1-PRODUCING AND FUMONISIN-B-1-NONPRODUCING FUSARIUM-MONILIFORME ISOLATES ARE SIMILAR - FUMONISIN-B-2 AND FUMONISIN-B-3 CAUSE HEPATOTOXICITY AND NEPHROTOXICITY IN RATS

Fumonisins are mycotoxins produced by Fusarium moniliforme, F. prolife ratum, and related Fusnarium species found on corn. They occur natural ly in corn-based feeds and foods and are suspected human esophageal ca rcinogens. Fumonisin B-1 (FB1), the most common homologue, causes the animal diseases associated with F: moniliforme. Hepato- and nephrotoxi cities, disrupted sphingolipid metabolism, and liver cancer have been found in rats fed FB1. To determine the in vivo effects of diets conta ining fumonisins B-2 (FB2) or B-3 (FB3), male rats were fed culture ma terials (CM) of FB1 non-producing F. moniliforme isolates to provide l ow (4.6-6.7 ppm), mid (32-49 ppm) or high (219-295 ppm) dietary levels of either FB2 (FB2CM) or FB3 (FB3CM). Other groups were fed culture m aterial of an FBI producing isolate (FB1CM) providing 6.9, 53 or 303 p pm total fumonisins (FB1 FB2 : FB3 = 1.0 : 0.38 : 0.15) and a tenth gr oup was fed a control diet having no detectable fumonisins. One-half ( n = 5/group) the animals were killed after three weeks, at which time the toxicological and histopathological effects of the three culture m aterials were similar, mimicked the effects of FBI, and included decre ased body weight gains, serum chemical indicators of hepatotoxicity, d ecreased kidney weights, and apoptosis of hepatocytes and kidney tubul ar epithelium. FB1CRM, FB2CM, and FB3CM affected sphingolipids, causin g increased sphinganine to sphingosine ratios (Sa/So) in both liver an d kidneys. The remaining animals (n = 5/group) were fed a control diet for three additional weeks. All body weight and tissue specific effec ts, including increased Sa/So, induced by the FB2CM, FB3CM and low lev el FB1CM diets were absent following the recovery period. Except for m ild biliary lesions found in the high dose FB1CM group and a few apopt otic hepatocytes present in one mid- and two high-dose FB1CM rats, no evidence of toxicity remained in these groups following the recovery p eriod.