TY - JOUR
T1 - The protective role of selenium on genetic damage and on cancer
AU - El-Bayoumy, Karam
N1 - Funding Information:
We thank Mrs. Patricia Sellazzo for preparing this manuscript and Mrs. Ilse Hoffmann for editing it. The work performed in the author’s laboratory and described in this manuscript was supported by the National Cancer Institute (USA), Grant nos. CA 46589, CA 70972 and DE 13222 from the National Institutes of Dental and Craniofacial Research (USA). This is manuscript no. 27 in the series: “Selenium in Chemoprevention of Carcinogenesis”.
PY - 2001/4/18
Y1 - 2001/4/18
N2 - Collectively, results from epidemiologic studies, laboratory bioassays, and human clinical intervention trials clearly support a protective role of selenium 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 considered as a primary event leading to neoplastic transformation. This report deals specifically with the evidence for a role of selenium in the inhibition of carcinogen-induced covalent DNA adduct formation and retardation of oxidative damage to DNA, lipids and proteins, and for modulating cellular and molecular events that are critical in cell growth inhibition and in the multi-step carcinogenesis process. At present, the bulk of our knowledge on the role of selenium on genetic stability is based primarily on animal data and from studies conducted in in vitro systems. Studies performed in vitro showed that the dose and form of selenium compounds are critical factors with regard to cellular responses. Inorganic (at doses up to 10 μM) and organic selenium compounds (at doses equal to or greater than 10 μM) elicit distinctly different cellular responses. The recommended daily allowance (RDA) is 50-70 μg Se per day for healthy adults; with 40 μg Se as minimum requirement. Less than 11 μg Se will definitely put people at risk of deficiency that would be expected to cause genetic damage. Daily doses of 100-200 μg Se inhibited genetic damage and cancer development in humans. About 400 μg 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 hypothesized 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 approach to inhibit genetic damage and the development of cancer. It is the author's recommendation that development of mechanism-based hypotheses that can be tested in pilot studies in different populations prior to a large-scale clinical trial in humans, is of paramount importance in order to better understand the role of selenium on genetic stability and cancer.
AB - Collectively, results from epidemiologic studies, laboratory bioassays, and human clinical intervention trials clearly support a protective role of selenium 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 considered as a primary event leading to neoplastic transformation. This report deals specifically with the evidence for a role of selenium in the inhibition of carcinogen-induced covalent DNA adduct formation and retardation of oxidative damage to DNA, lipids and proteins, and for modulating cellular and molecular events that are critical in cell growth inhibition and in the multi-step carcinogenesis process. At present, the bulk of our knowledge on the role of selenium on genetic stability is based primarily on animal data and from studies conducted in in vitro systems. Studies performed in vitro showed that the dose and form of selenium compounds are critical factors with regard to cellular responses. Inorganic (at doses up to 10 μM) and organic selenium compounds (at doses equal to or greater than 10 μM) elicit distinctly different cellular responses. The recommended daily allowance (RDA) is 50-70 μg Se per day for healthy adults; with 40 μg Se as minimum requirement. Less than 11 μg Se will definitely put people at risk of deficiency that would be expected to cause genetic damage. Daily doses of 100-200 μg Se inhibited genetic damage and cancer development in humans. About 400 μg 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 hypothesized 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 approach to inhibit genetic damage and the development of cancer. It is the author's recommendation that development of mechanism-based hypotheses that can be tested in pilot studies in different populations prior to a large-scale clinical trial in humans, is of paramount importance in order to better understand the role of selenium on genetic stability and cancer.
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U2 - 10.1016/S0027-5107(01)00075-6
DO - 10.1016/S0027-5107(01)00075-6
M3 - Review article
C2 - 11295158
AN - SCOPUS:0035906330
SN - 0027-5107
VL - 475
SP - 123
EP - 139
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -
