Interactions between aflatoxin B1 and dietary iron overload in hepatic mutagenesis

Toxicology. 2007 May 20;234(3):157-66. doi: 10.1016/j.tox.2007.02.009. Epub 2007 Feb 23.

Abstract

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 1 (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 microg AFB(1) for 10 days; group 4 (AFB(1)) was gavaged 25 microg 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 4-hydroxynonenal (4-HNE) and 8OHdG were observed in liver sections of the Fe+AFB(1) group, suggestive of multiplicative synergy. Significant levels of mutagenesis (p<0.001) 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.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aflatoxin B1 / toxicity*
  • Alanine Transaminase / blood
  • Aldehydes / metabolism
  • Animals
  • Aspartate Aminotransferases / blood
  • Cytokines / metabolism
  • DNA Damage
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Glutathione Transferase / metabolism
  • Immunohistochemistry
  • Iron / metabolism
  • Iron Overload / genetics*
  • Lipid Peroxides / metabolism
  • Liver / drug effects*
  • Liver / metabolism*
  • Liver / pathology
  • Mutagenesis / drug effects*
  • Mutagenicity Tests
  • Nitrates / metabolism
  • Nitrites / metabolism
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Superoxides / metabolism
  • Transferrin / metabolism

Substances

  • Aldehydes
  • Cytokines
  • Lipid Peroxides
  • Nitrates
  • Nitrites
  • Transferrin
  • Superoxides
  • 8-Hydroxy-2'-Deoxyguanosine
  • Aflatoxin B1
  • Iron
  • Glutathione Transferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Deoxyguanosine
  • 4-hydroxy-2-nonenal