The protective role of selenium on genetic damage and on cancer

Collectively, results from epidemiologic studies, laboratory bioassays, and human clinical intervention trials clearly support a protective role of se lenium against cancer development. Several hypotheses have been proposed to explain these observations. Increased genomic instability, either inherent or induced by exogenous agents (mutagens or carcinogens), has been conside red as a primary event leading to neoplastic transformation. This report de als specifically with the evidence for a role of selenium in the inhibition of carcinogen-induced covalent DNA adduct formation and retardation of oxi dative damage to DNA, lipids and proteins, and for modulating cellular and molecular events that are critical in cell growth inhibition and in the mul ti-step carcinogenesis process, At present, the bulk of our knowledge on th e role of selenium on genetic stability is based primarily on animal data a nd from studies conducted in in vitro systems. Studies performed in Vitro s howed that the dose and form of selenium compounds are critical factors wit h regard to cellular responses. Inorganic (at doses up to 10 muM) and organ ic selenium compounds (at doses equal to or greater than 10 muM) elicit dis tinctly different cellular responses. The recommended daily allowance (RDA) is 50-70 mug Se per day for healthy adults; with 40 mug Se as minimum requ irement. L ess than 11 mug Se will definitely put people at risk of deficie ncy that would be expected to cause genetic damage. Daily doses of 100-200 mug Se inhibited genetic damage and cancer development in humans. About 400 mug Se per day is considered an upper Limit. Clearly, doses above the RDA are needed to inhibit genetic damage and cancer. However, it has been hypot hesized that the intake of excessive doses of selenium may cause oxidative damage, leading to genomic instability. The use of a cocktail consisting of selenium and other vitamins and minerals appears to be a promising approac h to inhibit genetic damage and the development of cancer. It is the author 's recommendation that development of mechanism-based hypotheses that can b e tested in pilot studies in different populations prior to a large-scale c linical trial in humans, is of paramount importance in order to better unde rstand the role of selenium on genetic stability and cancer. (C) 2001 Elsev ier Science B.V. All rights reserved.