Wca. Gelderblom et al., Fumonisin-induced hepatocarcinogenesis: Mechanisms related to cancer initiation and promotion, ENVIR H PER, 109, 2001, pp. 291-300
We review the hepatocarcinogenic effects of fungal cultures of Fusarium ver
ticillioides(= Fusarium moniliforme) strain MRC 826 in male ED IX rats. Sub
sequent chemical analyses of the fumonisin B (FB) mycotoxin content in the
culture material used and long-term carcinogenesis studies with purified FB
1 provide information about dose-response effects, relevance of hepatotoxic
ity during FB1-induced carcinogenesis, and the existence of a no-effect thr
eshold. Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body w
eight (bw)/day over approximately 2 years produce liver cancer in male ED I
X rats. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, al
though mild toxic and preneoplastic lesions are induced. The nutritional st
atus of the diets used in the long-term experiments was marginally deficien
t in lipotropes and vitamins and could have played an important modulating
role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a can
cer initiation/promotion model in rat liver provided important information
about the possible mechanisms involved during the initial stages of cancer
development by this apparently nongenotoxic mycotoxin. These studies suppor
ted the findings of long-term investigations indicating that a cytotoxic/pr
oliferative response is required for cancer induction and that a no-effect
threshold exists for cancer induction. The mechanisms proposed far cancer i
nduction are highlighted and include the possible role of oxidative damage
during initiation and the disruption of lipid metabolism, integrity of cell
ular membranes, and altered growth-regulatory responses as important events
during promotion.