Decrease of manganese superoxide dismutase activity in rats fed high levels of iron during colon carcinogenesis.

Abstract

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known to decrease manganese superoxide dismutase (MnSOD) activity in colonic mucosa. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is absent or decreased in most tumours, including those from the colon. This study was designed to determine the effects of high dietary lipid and iron levels on MnSOD activity during the early weeks of colon carcinogenesis. Male Fischer-344 rats were fed 20% lipid diets of either corn oil or menhaden oil containing adequate iron (35 mg/kg) or supplemental iron (535 mg/kg). Rats from each diet were divided into carcinogen treatment groups and given two weekly injections of either azoxymethane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collected 1, 6 and 12 wk following injections and analysed for MnSOD activity, mineral concentration and nuclear aberrations. Results showed that iron supplementation increased nuclear aberrations, and decreased manganese concentration and MnSOD activity in colonic mucosa ot control animals. AOM, and interaction of iron and AOM, also decreased MnSOD activity. A decrease in the activity of this enzyme during carcinogenesis may be one mechanism whereby these dietary factors ultimately increase tumour risk.