High Dietary Intake of Sodium Selenite Does Not Affect Gene Mutation Frequency in Rat Colon and Liver

• Published in: Biological trace element research 2009-10, Vol.131 (1), p.71-80
• Main Authors: Zeng, Huawei, Uthus, Eric O, Ross, Sharon A, Davis, Cindy D
• Format: Article
• Language: English
• Subjects: Animal models; Animals; anticarcinogenic activity; Biochemistry; Biomedical and Life Sciences; Biotechnology; Body weight; colon; Colon - drug effects; Colon - metabolism; Colon cancer; Colonic Neoplasms - chemically induced; Colonic Neoplasms - genetics; Colonic Neoplasms - prevention & control; Colorectal cancer; Data processing; Deoxyribonucleic acid; Diet; Dietary intake; Diets; Dimethylhydrazines - toxicity; DNA; DNA damage; enzyme activity; Etiology; gene mutation frequency; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Lesions; Life Sciences; Liver; Liver - drug effects; Liver - metabolism; Mucosa; mutagenesis; Mutation; Mutation - drug effects; nutrient intake; Nutrition; Oncology; Point mutation; protective effect; Rats; Rodents; selenite; selenites; Selenium; Sodium selenite; Sodium Selenite - administration & dosage; Sodium Selenite - pharmacology; Thioredoxin-disulfide reductase; Transcription Factors; Transgenic animals
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-009-8348-3

Our previous studies have shown that selenium (Se) is protective against dimethylhydrazine (DMH)-induced preneoplastic colon cancer lesions, and protection against DNA damage has been hypothesized to be one mechanism for the anticancer effect of Se. The present study was designed to determine whether dietary selenite affects somatic mutation frequency in vivo. We used the Big Blue transgenic model to evaluate the in vivo mutation frequency of the cII gene in rats fed either a Se-deficient (0 μg Se/g diet) or Se-supplemented diet (0.2 or 2 μg Se/g diet; n = 3 rats/diet in experiment 1 and n = 5 rats/group in experiment 2) and injected with DMH (25 mg/kg body weight, i.p.). There were no significant differences in body weight between the Se-deficient and Se-supplemented (0.2 or 2 μg Se/g diet) rats, but the activities of liver glutathione peroxidase and thioredoxin reductase and concentration of liver Se were significantly lower (p < 0.0001) in Se-deficient rats compared to rats supplemented with Se. We found no effect of dietary Se on liver 8-hydroxy-2'-deoxyguanosine. Gene mutation frequency was significantly lower in liver (p < 0.001) than that of colon regardless of dietary Se. However, there were no differences in gene mutation frequency in DNA from colon mucosa or liver from rats fed the Se-deficient diet compared to those fed the Se-supplemented (0.2 or 2 μg Se/g diet) diet. Although gene mutations have been implicated in the etiology of cancer, our data suggest that decreasing gene mutation is not likely a key mechanism through which dietary selenite exerts its anticancer action against DMH-induced preneoplastic colon cancer lesions in a Big Blue transgenic rat model.