THE CANCER-PROMOTING POTENTIAL OF FUMONISIN B-1 IN RAT-LIVER USING DIETHYLNITROSAMINE AS A CANCER INITIATOR

The cancer-promoting potential of fumonisin B-1 (FB1) was investigated by feeding different dietary levels (10, 50, 100, 250, 500 mg FB1/kg) to diethynitrosamine (DEN)-initiated rats for 21 days. Dietary levels containing 50 mg FB1/kg and higher, markedly increased the number and size of the placental form of glutathione-S-transferase-positive (GST P(+)) foci in the liver of the rats. The cancer-promoting activity of FB1 was associated with an inhibitory effect on partial hepatectomy (P H)-induced regenerative hepatocyte proliferation, as the incorporation of H-3-labelled thymidine was significantly (P < 0.05) reduced by tho se FB1-containing diets that exhibited cancer promotion. In vitro stud ies on the mitogenic activity of epidermal growth factor (EGF) in prim ary rat hepatocytes further supported the in vivo data in that FB1, si milar to other cancer promoters such as phenobarbital and 2-acetylamin ofluorene (2-AAF), alters growth stimulatory responses in primary hepa tocytes. No significant (P > 0 05) changes in the sphinganine/sphingos ine (Sa/So) ratio were observed in the liver of the rats fed the lowes t FB1-containing diet (50 mg FB1/kg diet) that effected cancer promoti on. The present study indicated that FB1 exhibited cancer-promoting ac tivity in the absence of adverse hepatotoxic effects and at dietary le vels that failed to effect cancer initiation.