Epigenetic effects of folic acid in colorectal carcinogenesis induced by MNNG in rats

Abstract

Estimates for the year 2010 in Brazil, indicate colorectal cancer as the third most common cancer worldwide in both gender. Low folate status is known as a cancer and cardiovascular disease risk factor.Observational studies reported that elevated plasmatic or dietetic folate levels can have chemopreventive properties for these conditions. Nevertheless, recent intervention studies suggest that folate supplementation can increase the risk for these chronic diseases. Data provided by experimental studies suggest that folate has dual modulatory effects in the development and progression of colorectal cancer, dependind on time and dose of the folate intervention. This latter view has gained considerable interest in the context of madatory fortification and became a public health problem. Recent evidences from Chile, Canada and USA suggest that folate fortification is associated with an additional colon cancer risk. Folic acid has an important role in DNA metilation and cellular homeostasis and the folate deficiency can result in a variety of cellular consequences, including uracil misincorporation during DNA synthesis, resulting in a spontaneous mutations increase, chromossomal abnormalities and in DNA erroneous synthesis. DNA and histones metilation are epigenetic modifications that are important transcription and gene silencing determinants. Otherwise, there isn´t yet a clear relation between folic acid fortification and protection agaisnt supressor genes mutations in the colorectal mucosa in literarture and its positive effects in cellular death and proliferation haven´t been totally confirmed. (AU)