Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis

Background/aim: Dietary aflatoxin B-1 (AFB(1)) exposure and iron overload are important causes of hepatocellular carcinoma in sub-Saharan Africa. The aim of this study was to investigate if the two risk factors have an interactive effect. Methods: Four groups of Wistar albino rats were studied for 12 months. Group I (control) was fed the normal chow diet; group 2 (Fe) was supplemented with 0.75% ferrocene iron; group 3 (Fe + AFB(1)) was fed 0.75% ferrocene throughout and gavaged 25 mu g AFB(1) for 10 days; group 4 (AFB(1)) was gavaged 25 mu g AFB(1) for 10 days. Iron profile, lipid peroxidation (LPO), 8-hydroxydeoxyguanosine (8OHdG), oxidative lipid/DNA damage immunohistochemistry, superoxide/nitrite free radicals, cytokines IL6, IL- 10, transaminases (ALT/AST) and Ames mutagenesis tests were performed. Results: LPO and ALT showed a significant (p < 0.05)/additive effect and 8OHdG a significant (p < 0.05)/multiplicative effect in the Fe + AFB(1) group. IL-6 produced a negative synergy as against an additive antagonistic effect with IL- 10. Massive deposits of 4hydroxynonenal (4-HNE) and 8OHdG were observed in liver sections of the Fe + AFB(1) group, suggestive of multiplicative synergy. Significant levels of mutagenesis (p < 0.00 1) were observed in the Fe + AFB(1) group. This multiplicative synergy was five-fold. Conclusion: Dietary iron overload and AFB(1) have a multiplicative effect on mutagenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.