Fumonisin B(1) (FB(1)), 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 (CCl(4)) and direct
mitogen-induced
hyperplasia, induced by
lead nitrate (PbNO(3)), on FB(1)-induced
cancer initiation. Initiation was effected over a period of 14 days by gavage administration of FB(1) at different daily doses ranging from 0.14 to 3.5 mg FB(1)/100 g
body weight while the stimuli for cell proliferation were introduced 7 days after the start of the FB(1) 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 CCl(4) on day 4.
Cancer initiation by FB(1) was associated with a hepatotoxic effect and an increase in lipid peroxidation. In contrast to compensatory liver cell proliferation induced by PH and CCl(4),
mitogen-induced
hyperplasia (PbNO(3)) failed to enhance the
cancer initiating potential of FB(1) 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 FB(1) is required in assessing the risks posed by this
mycotoxin to humans.