The effects of dietary iron overload on fumonisin B1-induced cancer promotion in the rat liver.

Abstract

The present study was performed to determine whether excess hepatic iron modulates the cancer-initiating and promoting properties of FB1. Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) control diet (AIN, n = 8); (ii) FB1 250 mg/kg diet (FB1, n = 10); (iii) 1-2% carbonyl 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-loaded animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 micromol/g dry weight (FB1/CI) (mean +/- SEM). All the FB1-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine transaminase (ALT) levels. FB1 appeared to augment iron-induced hepatic lipid peroxidation, 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 'enzyme-altered' foci and nodules per cm2 (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (%) of liver occupied by foci and nodules (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB1/CI. The addition of FB1 to dietary iron loading caused a shift in distribution of iron from hepatocytes to Kupffer cells, probably due to phagocytosis of necrotic iron-loaded hepatocytes. In conclusion, (i) FB1 appears to cause toxicity 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 properties of FB1, possibly due to a stimulatory effect of iron on hepatocyte regeneration.

• Authors: E R Lemmer, W C Gelderblom, E G Shephard, S Abel, B L Seymour, J P Cruse, R E Kirsch, W F Marasas, P M Hall
• Journal: Cancer letters (Cancer Lett) Vol. 146 Issue 2 Pg. 207-15 (Nov 15 1999) ISSN: 0304-3835 [Print] Ireland
• PMID: 10656628 (Publication Type: Journal Article)

Chemical References

• Carboxylic Acids
• Carcinogens, Environmental
• Fumonisins
• Isoenzymes
• fumonisin B1
• Glutathione S-Transferase pi
• Glutathione Transferase
• Gstp1 protein, rat

Topics

• Animals
• Carboxylic Acids (toxicity)
• Carcinogens, Environmental (toxicity)
• Fumonisins
• Glutathione S-Transferase pi
• Glutathione Transferase (metabolism)
• Iron Overload (physiopathology)
• Isoenzymes (metabolism)
• Lipid Peroxidation
• Liver (metabolism, pathology)
• Liver Neoplasms, Experimental (chemically induced, pathology, prevention & control)
• Male
• Organ Size
• Rats
• Rats, Inbred F344
• Weight Gain