Cancer initiation by fumonisin B1 in rat liver – role of cell proliferation

Fumonisin B1 (FB1), a carcinogenic mycotoxin produced by the fungus Fusarium verticillioides in corn, causes cancer initiation in rat liver in a similar manner to genotoxic carcinogens although apparently with different kinetics. The present experiment was designed to evaluate the role of regenerative cell proliferation, effected by partial hepatectomy (PH) and carbontetrachloride (CCl4) and direct mitogen-induced hyperplasia, induced by lead nitrate (PbNO3), on FB1-induced cancer initiation. Initiation was effected over a period of 14 days by gavage administration of FB1 at different daily doses ranging from 0.14 to 3.5 mg FB1/100 g body weight while the stimuli for cell proliferation were introduced 7 days after the start of the FB1 treatment. Based on the proliferative stimulus used, cancer promotion was effected 3 weeks after completion of the initiating treatment by 2-acetylaminofluorene (2-AAF) treatment followed by PH or carbon tetrachloride CCl4 on day 4. Cancer initiation by FB1 was associated with a hepatotoxic effect and an increase in lipid peroxidation. In contrast to compensatory liver cell proliferation induced by PH and CCl4, mitogen-induced hyperplasia (PbNO3) failed to enhance the cancer initiating potential of FB1 suggesting that cancer induction by a non-genotoxic carcinogen is supported by regenerative cell proliferation. Cognizance of the enhancing role of cell proliferation during cancer initiation by FB1 is required in assessing the risks posed by this mycotoxin to humans.