DECREASE OF MANGANESE SUPEROXIDE-DISMUTASE ACTIVITY IN RATS FED HIGH-LEVELS OF IRON DURING COLON CARCINOGENESIS

Diets high in fat or iron have been associated with an increased risk for development of colon cancer. These two dietary factors are known t o decrease manganese superoxide dismutase (MnSOD) activity in colonic mucose. MnSOD is an antioxidant enzyme that protects mitochondria from oxygen radical damage. MnSOD has tumour suppressive activity and is a bsent or decreased in most tumours, including those from the colon. Th is study was designed to determine the effects of high dietary lipid a nd iron levels on MnSOD activity during the early weeks bf colon carci nogenesis. Male Fischer-344 rats were fed 20% lipid diets of either co rn oil or menhaden oil containing adequate iron (35 mg/kg) or suppleme ntal iron (535 mg/kg). Rats from each diet were divided into carcinoge n treatment groups and given two weekly injections of either azoxymeth ane (AOM) at a dose of 12 mg/kg, or saline. Mucosal tissue was collect ed 1, 6 and 12 wk following injections and analysed for MnSOD activity , mineral concentration and nuclear aberrations. Results showed that i ron supplementation increased nuclear aberrations, and decreased manga nese concentration and MnSOD activity in colonic mucosa of control ani mals. AOM, and interaction of iron and AOM, also decreased MnSOD activ ity. A decrease in the activity of this enzyme during carcinogenesis m ay be one mechanism whereby these dietary factors ultimately increase tumour risk. (C) 1998 Elsevier Science Ltd.. All rights reserved.