ABSTRACT
Alcohol is an environmental toxicant that is associated with several major human diseases because it has harmful effects on many different tissues and organs. Alcohol effects cellular toxicity by several mechanisms, mainly through acetaldehyde, the rst metabolite produced during ethanol degradation, and through the formation of reactive oxygen species (ROS). Acetaldehyde interferes with DNA synthesis and repair mechanisms and is well recognized as playing a role in cancer of upper and lower gastrointestinal tract. Meanwhile, the hazardous effects of alcohol on the liver are more likely to be mediated by oxidative stress (Poschl and Seitz, 2004; Dey and Cederbaum, 2006; Seitz and Stickel, 2007). Several studies have also demonstrated that alcohol impairs one-carbon metabolism leading to an aberrant methyl group transfer, and it is believed that this molecular event may play a role in the development of cancer and other alcohol-related diseases. In this chapter, we focused on the effects of alcohol on one-carbon metabolism and its inuence on DNA methylation,
6.1 Introduction .................................................................................................. 179 6.2 Effects of Alcohol on One-Carbon Metabolism ........................................... 181 6.3 Effects of Alcohol on DNA Methyltransferases ........................................... 183 6.4 Alcohol Affects Fetal Growth and Neuronal Development through
DNA Methylation ......................................................................................... 183 6.4.1 Preconceptional and Preimplantational Maternal Alcohol Exposure ... 184 6.4.2 Alcohol Exposure during Gastrulation and Early Neurulation ........ 184 6.4.3 Paternal Alcohol Exposure ............................................................... 186
6.5 Alcohol Affects Carcinogenesis through DNA Methylation ........................ 187 6.5.1 Liver Cancer ..................................................................................... 187 6.5.2 Colorectal Cancer ............................................................................. 188 6.5.3 Head and Neck Cancer ..................................................................... 188 6.5.4 Breast Cancer .................................................................................... 189
6.6 Alcoholism, Alcohol Abuse, and DNA Methylation .................................... 189 6.7 Conclusions ................................................................................................... 191 References .............................................................................................................. 191
which could be one of the mechanisms involved in the epigenetic effects of alcohol (Christensen and Marsit, 2011; Kim et al., 2012).
