82 - DNA Damage Resulting from Alcohol Abuse with Special Reference to the Brain

Abstract

This chapter focuses on the role of Deoxyribonucleic acid (DNA) damage resulting from alcohol abuse in relation to alcohol related health effects, with a special focus on the nervous system. It is clear that alcohol abuse can result in a myriad of health problems, including liver and brain damage, fetal alcohol effects, and an increased risk of certain types of cancers. A major mechanism by which alcohol abuse can cause damage to DNA is generation of acetaldehyde, a known genotoxin and carcinogen. Acetaldehyde forms specific DNA adducts and DNA-protein crosslinks. The ethanol molecule itself can form hydroxyethyl radicals, which can react with DNA to form DNA adducts. Also, alcohol creates a state of oxidative stress in cells, resulting in elevated levels of Reactive Oxygen Species (ROS). ROS causes DNA base lesions and strand breaks in the DNA, and stimulate the generation of lipid peroxidation products, which also forms DNA adducts. Alcohol has powerful effects on the mitochondria, and has been shown in several systems to cause mitochondrial DNA damage. In addition, the damaging effects of alcohol on mitochondria could potentially cause leakage of ROS out of the mitochondria, leading to nuclear DNA damage.