Fed before diethylnitrosamine, Fusarium moniliforme and F proliferatum mycotoxins alter the persistence of placental glutathione S-transferase-positive hepatocytes in rats.

Groups of 5-w-old F344/N female rats were fed a semipurified diet for 13 w with or without 20 mg fumonisin B1/kg provided from an aqueous extract of Fusarium moniliforme-corn culture. After 1 w, a single dose of 30 mg diethylnitrosamine (DEN)/kg was given orally. Twelve weeks later, the presence of placental glutathione S-transferase-positive (PGST-[+]) hepatocytes were immunohistochemically quantified. Rats given DEN and the FB1-containing diet for 1 or 13 w developed 4-fold more PGST-[+] hepatocytes than rats given DEN alone. In a second study, male and female F344/N rats were fed 20 mg purified FB1/kg diet or F proliferatum-corn culture material containing 20 mg FB1/kg diet for 1 w before DEN treatment. One week after DEN treatment, male rats fed the F proliferatum-corn culture material had significantly fewer PGST-[+] hepatocytes than those fed DEN with or without purified FB1. At 9 w after DEN treatment, PGST-[+] cells in female rats given DEN and fed F proliferatum-corn culture material were more persistent than in rats given DEN alone. Males given DEN and fed FB1 or F proliferatum culture material had significantly fewer PGST-[+] hepatocytes than males given DEN alone. These results suggest that F moniliforme and F proliferatum components are cocarcinogens in females. In males, however, FB1 and unidentified F proliferatum components reduced the persistence of DEN-initiated preneoplastic hepatocytes.