The Effects of Diet, Genetics and Chemicals on Toxicity and Aberrant DNA Methylation: an Introduction

摘要: In the early 1930s, group of Banting and Best showed that choline moiety lecithin was responsible for prevention fatty livers produced in pancreatectomized dogs treated with insulin. This first study linking abnormal methyl metabolism disease. Since then, deficiencies each four essential dietary sources groups (choline, methionine, vitamin B-12 folic acid) have been associated increased risk a number diseases. Choline-deficient diets were shown to enhance liver tumor formation rats, such frequently found lead atherosclerosis. Although methionine deficiency per se not extensively studied vivo, its metabolic antagonist ethionine did cause cancer pancreatic toxicity rodents. Deficiencies acid long neurological disturbances birth defects both humans experimental animals. 1969 inborn errors leading accumulation demethylated metabolite homocysteine, proposed as contributing onset Before 1990, numerous studies described methylation DNA tumors transformed cells. Less investigated, however, exogenous endogenous agents methylation. These included genetic variants among rodent strains methyl-deficient caused cancer. addition, several chemicals, particularly carcinogens, alter The possible links between chemically induced alterations development other diseases little explored. However, by chain causality had established carcinogenesis insufficiency well specific genes. Also during this period, diminished activity enzyme methylenetetrahydrofolate reductase (EC 1.5.1.20), which is actual de novo synthesis groups, be developing atherosclerosis, disorders defects. exponential rise on since then enables us examine here extent mechanisms processes seem exert their toxic effects one disease may applicable pathologies.