Er. Lemmer et al., The effects of dietary iron overload on fumonisin B-1-induced cancer promotion in the rat liver, CANCER LETT, 146(2), 1999, pp. 207-215
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.