Cancer initiating properties of fumonisin B1 in a short-term rat liver carcinogenesis assay

The nature of cancer initiation by fumonisin B-1 (FB1) was investigated in rat liver by monitoring the effect of phenobarbital (PB) as cancer promoter and evaluating the involvement of spontaneously initiated cells. A PB promoting regimen (0.05% in the diet) stimulated the outgrowth of FB1-induced placental glutathione S-transferase (GSTP) positive initiated hepatocytes. Reversion of the FB1-induced GSTP(+) foci was noticed in the absence of a promoting regimen. Younger rats were shown to be more sensitive to the induction of GSTP(+) foci by FB1. Cancer initiation by FB1 was associated with a hepatotoxic effect, which was less pronounced in older rats presumably due to a reduced intake. A specific role of spontaneously initiated cells and their promotion by FB1 into the development of eosinophilic clear cell foci could not be established under the present experimental conditions. The ability of different stimuli to selectively promote the outgrowth of FB1 initiated cells further verifies the cancer initiating potency of this apparent nongenotoxic mycotoxin. The underlying mechanism(s) involved in the genesis of the initiated hepatocytes is not known at present. (C) 2008 Elsevier Ireland Ltd. All rights reserved.