The Role of Molybdenum Hydroxylase Generated Free Radicals in Alcohol Induced Breast Cancer

Abstract

Abstract : The breakdown of alcohol may contribute to the risk for breast cancer (BC) through the generation of toxic by-products of oxygen, (reactive oxygen species, ROS) that can produce the DNA mutations and chromosome damage found in BC. ROS can be evolved stochiometrically from cytochrome P45O-El 1 (CYP-El 1) in the first step of alcohol degradation and subsequently by the action of xanthine oxidoreductase (XOR) and aldehyde oxidase (AOX) that consume acetaldehyde and NADH. We have proposed that these enzymes in the breast are responsible for the formation of ROS following alcohol consumption, and we suggest that ROS derived from alcohol will produce the DNA mutations and chromosome damage that lead to breast cancer. Our studies have shown that breast tissue expresses substantial levels of CYP-E1 1, XOR, and AOX. Furthermore, our recent studies have demonstrated that the genes encoding XOR and AOX are activated by cytokines and growth factors known to have significant affects on the mammary gland. Cytokine stimulated cultured epithelial cells produced ROS that could be blocked by inhibitors of XOR, hence activation of these enzymes generates intracellular RO S. We suggest that activation of RO S generating genes in the breast may contribute to alcohol mediated ROS toxicity leading to BC.