The effects of dietary iron overload on fumonisin B-1-induced cancer promotion in the rat liver

The present study was performed to determine whether excess hepatic iron mo dulates the cancer-initiating and promoting properties of FB1. Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) contro l diet (AIN, n = 8); (ii) FB1 250 mg/kg diet (FB1, n = 10); (iii) 1-2% carb onyl iron (CI, n = 10); or (iv) FB1 plus iron loading (FB1/CI, n = 10) for 5 weeks (2 x 2 factorial design). Hepatic iron concentrations in iron-loade d animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 mu mol/g dry weigh t (FB1/CI) (mean +/- SEM). AU the FB1-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine tran saminase (ALT) levels. FB1 appeared to augment iron-induced hepatic lipid p eroxidation, as measured by the generation of thiobarbituric acid reacting substances (TBARS) in liver homogenates (P < 0.0001). Morphometric analysis showed that FB1 caused a significantly greater mean +/- SEM number of 'enz yme-altered' foci and nodules per cm(2) (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (4b) of liver occupied by foci and nodu les (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB1/CI. T he addition of FB1 to dietary iron loading caused a shift in distribution o f iron from hepatocytes to Kupffer cells, probably due to phagocytosis of n ecrotic iron-loaded hepatocytes. In conclusion, (i) FB1 appears to cause to xicity in the liver independently from effects on lipid peroxidation; (ii) FB1 has a potentiating effect on iron-induced lipid peroxidation; and (iii) dietary iron loading appears to protect against the cancer promoting prope rties of FB1, possibly due to a stimulatory effect of iron on hepatocyte re generation. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.