The
trace element nutrient
selenium (Se) discharges its well-known nutritional
antioxidant activity through the Se-dependent
glutathione peroxidases. It also regulates nuclear factor activities by redox mechanisms through the
selenoprotein thioredoxin reductases. Converging data from epidemiological, ecological, and clinical studies have shown that Se can decrease the risk for some types of human
cancers, especially those of the prostate, lung, and colon. Mechanistic studies have indicated that the
methylselenol metabolite pool has many desirable attributes of
chemoprevention, targeting both
cancer cells and vascular endothelial cells, whereas the
hydrogen selenide pool in excess of
selenoprotein synthesis can lead to
DNA single strand breaks, which may be mediated by some
reactive oxygen species. We propose a new paradigm based on a consideration of the post-initiation biology of avascular early lesion expansion microenvironment, physiochemistry of Se delivery, and the obligatory need for angiogenesis to sustain lesion progression. Our model integrates the roles of
selenoproteins and specific Se metabolites to account for
cancer risk reduction or enhancement. For future studies, speciation (profiling) methods for Se metabolites and for Se forms in foods and supplements are much needed for hypothesis testing and for the development of mechanism-based Se status markers for
cancer prevention. Randomized
cancer prevention trials are necessary to test the efficacy of methyl
selenium compounds.