Nutrition and DNA Repair - Potential Molecular Mechanisms of Action
J.C. Mathers, J.M. Coxhead and J. Tyson
Affiliation: Human Nutrition Research Centre, School of Clinical Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
At its most fundamental, cancer is a genetic disease in the sense that the primary events in tumorigenesis involve damage to the genome. The genome is subject to damage continuously from both exogenous agents and endogenous processes but this becomes functionally important only if the damage is not detected and resolved in a timely and effective manner. In mammals there are 5 DNA repair pathways, encoded by approximately 150 genes, which appear to have arisen early in evolution and which are highly conserved. Given the substantial epidemiological and experimental evidence that variation in dietary intake accounts for a significant proportion of the variance in cancer prevalence, an a priori case can be made that dietary factors may influence the effectiveness of DNA repair. A review of the literature has identified 4 observational and 8 intervention studies in human subjects where DNA repair (or a component thereof) has been measured in relation to nutrition. This rather limited evidence base precludes drawing definitive conclusions, but the fact that there were significant effects of dietary supplements in 5 out of the 8 intervention studies suggests that food components and/or nutritional status may influence DNA repair. This review considers possible molecular mechanisms through which such factors could modulate repair.
Keywords: DNA repair, DNA damage, DNA methylation, mitochondrial DNA, nutrients, folate, selenium, gene expression, zinc finger proteins
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