Ka. Voss et al., An overview of rodent toxicities: Liver and kidney effects of fumonisins and Fusarium moniliforme, ENVIR H PER, 109, 2001, pp. 259-266
Fumonisins are produced by Fusarium moniliforme (= F. verticillioides) and
other Fusarium that grow on corn worldwide. They cause fatal toxicoses of h
orses and swine. Their effects in humans are unclear, but epidemiologic evi
dence suggests that consumption of fumonisin-contaminated corn contributes
to human esophageal cancer in southern Africa and China. Much has been lear
ned from rodent studies about fumonisin B-1 (FB1), the most common homologu
e. FB, is pearly absorbed and rapidly eliminated in feces. Minor amounts ar
e retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause
the same liver cancer promotion and subchronic (studies less than or equal
to 90 days) liver and kidney effects as F. moniliforme. FB1 induces apoptos
is of hepatocytes and of proximal tubule epithelial cells. More advanced le
sions in both organs are characterized by simultaneous cell loss (apoptosis
and necrosis) and proliferation (mitosis). Microscopic and other findings
suggest that an imbalance between cell loss and replacement develops, a con
dition favorable for carcinogenesis. On the molecular level, fumonisins inh
ibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretica
lly, sphingolipid-mediated regulatory processes that influence apoptosis an
d mitosis. Liver sphingolipid effects and toxicity are correlated, and cera
mide synthase inhibition occurs in liver and kidney at doses below their re
spective no-observed-effect levels. FB1 does not cross the placenta and is
not teratogenic in vivo in rats, mice, or rabbits, but is embryotoxic at hi
gh, maternally toxic doses. These data have contributed to preliminary risk
evaluation and to protocol development for carcinogenicity and chronic tox
icity studies of FB1 in rats and mice.