High dietary intake of sodium selenite induces oxidative DNA damage in rat liver.
One mechanism for the cancer-chemopreventive effects of high selenium (Se) intake is hypothesized to be antioxidant protection of DNA. In this work we examine DNA oxidation in whole animals as a function of dietary Se intake and carcinogen administration. Weanling male Sprague-Dawley rats were fed a basal, Torula yeast-based, Se-deficient diet supplemented with 0, 0.15, or 2.0 ppm Se as sodium selenite for 10 wk. They were then injected with 0, 0.1, or 10 mg /kg body weight of the pro-oxidant carcinogen N-nitrosodiethylamine. High levels of carcinogen and high levels of selenite intake each increased concentration of 8-hydroxy-2'-deoxyguanosine in liver DNA. Se-dependent glutathione peroxidase I gene expression and enzyme activity were dramatically reduced by dietary Se deficiency but were unaffected by carcinogen administration. There were no significant main or interactive effects of Se or carcinogen on activity or gene expression of the DNA repair enzyme 8-oxoguanine glycosylase I. These results do not support the hypothesis that high Se intake may be cancer-preventive by inhibiting oxidative DNA damage. Rather than inhibiting oxidative DNA damage, these findings suggest that high dietary intake of inorganic Se may promote in vivo DNA oxidation.
Wycherly
Benjamin J
BJ
Department of Nutrition, Dietetics, and Food Science, Brigham young, University, Provo, Utaah 84602, USA.
Moak
Michael A
MA
Christensen
Merrill J
MJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019587:Dietary Supplements; D004052:Diethylnitrosamine / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D010084:Oxidation-Reduction; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018038:Sodium Selenite / Q000008:administration & dosage* / Q000494:pharmacology
D002273:Carcinogens; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D005979:Glutathione Peroxidase; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D003849:Deoxyguanosine; D018038:Sodium Selenite