Cancer initiation by fumonisin B-1 in rat liver - role of cell proliferation

Fumonisin B-1 (FB1), a carcinogenic mycotoxin produced by the fungus Fusari um verticillioides in corn, causes cancer initiation in rat liver in a simi lar manner to genotoxic carcinogens although apparently with different kine tics. The present experiment was designed to evaluate the role of regenerat ive cell proliferation, effected by partial hepatectomy (PH) and carbontetr achloride (CCl4) and direct mitogen-induced hyperplasia, induced by lead ni trate (PbNO3), on FB1-induced cancer initiation. Initiation was effected ov er a period of 14 days by gavage administration of FB1 at different daily d oses ranging from 0.14 to 3.5 mg FB1/100 g body weight while the stimuli fo r cell proliferation were introduced 7 days after the start of the FB1 trea tment, Based on the proliferative stimulus used, cancer promotion was effec ted 3 weeks after completion of the initiating treatment by 2-acetylaminofl uorene (2-AAF) treatment followed by PH or carbon tetrachloride CCl4 on day 4. Cancer initiation by FB1 was associated with a hepatotoxic effect and a n increase in lipid peroxidation, In contrast to compensatory liver cell pr oliferation induced by PH and CCl4, mitogen-induced hyperplasia (PbNO3) fai led to enhance the cancer initiating potential of FB1 suggesting that cance r induction by a non-genotoxic carcinogen is supported by regenerative cell proliferation. Cognizance of the enhancing role of cell proliferation duri ng cancer initiation by FB1 is required in assessing the risks posed by thi s mycotoxin to humans. (C) 2001 Elsevier Science Ireland Ltd. All rights re served.