Abstract
Supplementation of the culture media of human MCF-7 breast carcinoma cells or mouse fibroblasts with low levels of selenium (30 nM) provided as sodium selenite was shown to protect these cells from ultraviolet (UV)-induced chromosome damage, as quantified by micronucleus assay. Selenium supplementation was also effective in reducing UV-induced gene mutations as measured in the lacI shuttle vector model. Protection was dependent on functional BRCA1 activity, a protein implicated in breast cancer risk and DNA damage repair. In addition, overexpression of GPx-1, a selenoprotein with antioxidant activity, also attenuated UVinduced micronuclei formation in the absence of selenium supplementation. Combining selenium supplementation with GPx-1 overexpression further reduced UV-induced micronucleus frequency. These data provide evidence that the benefits of selenium supplementation might be either through the prevention or repair of DNA damage, and they implicate at least one selenoprotein (GPx-1) in the process.
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K. El-Bayoumy, The role of selenium in cancer prevention, in V. T. De Vita, S. Hellman, and R. A. Rosenberg, eds., Cancer Prevention, J. B. Lippincott, Philadelphia, Co., pp. 1–15 (1991).
D. L. Hatfield and V. N. Gladyshev, How selenium has altered our understanding of the genetic code, Mol. Cell. Biol. 22, 3565–3576 (2002).
G. V. Kryukov, S. Castellano, S. V. Novoselov, et al., Characterization of mammalian selenoproteomes, Science 300, 1439–1443 (2003).
D. Ratnasinghe, J. A. Tangrea, M. R. Andersen, et al., Glutathione peroxidase codon 198 polymorphism variant increases lung cancer risk, Cancer Res. 60, 6381–6383 (2000).
Y. Ichimura, T. Habuchi, N. Tsuchiya, et al., Inreased risk of bladder cancer associated with a glutathione peroxidase 1 codon 198 variant, J. Urol. 172, 728–732 (2004).
Z. Kote-Jarai, F. Durocher, S. M. Edwards, et al., Association between the GCG polymorphism of the selenium dependent GPX1 gene and the risk of young onset prostate cancer, Prostate Cancer Prostatic Dis. 5, 189–192, (2002).
Y. J. Hu and A. M. Diamond, Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium, Cancer Res. 63, 3347–3351 (2003).
Y. J. Hu, M. E. Dolan, R. Bae, et al., Allelic loss at the GPx-1 locus in cancer of the head and neck, Biol. Trace Element Res. 101, 97–106 (2004).
Y. Hu, R. V. Benya, R. E. Carroll, and A. M. Diamond, Allelic loss of the gene for the GPX1 selenium-containing protein is a common event in cancer, J. Nutr. 135, 3021S-3024S (2005).
J. A. Moscow, L. Schmidt, D. T. Ingram, J. Gnarra, B. Johnson, and K. H. Cowan, Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer, Carcinogenesis 15, 2769–2773 (1994).
A. M. Diamond, P. Dale, J. L. Murray, and D. J. Grdina, The inhibition of radiationinduced mutagenesis by the combined effects of selenium and the aminothiol WR-1065, Mutat. Res. 356, 147–154 (1996).
Y. R. Seo, C. Sweeney, and M. L. Smith, Selenomethionine induction of DNA repair response in human fibroblasts, Oncogene 21, 3663–3669 (2002).
D. J. Waters, S. Shen, L. T. Glickman, et al., Prostate cancer risk and DNA damage: translational significance of selenium supplementation in a canine model, Carcinogenesis 26, 1256–1262 (2005).
B. L. Samuels, J. L. Murray, M. B. Cohen, et al., Increased glutathione peroxidase activity in a human sarcoma cell line with inherent doxorubicin resistance, Cancer Res. 51, 521–527 (1991).
M. Fenech and A. A. Morley, Measurement of micronuclei in lymphocytes, Mutat. Res. 147, 29–36 (1985).
J. L. Fischer, J. K. Lancia, A. Mathur, and M. L. Smith, Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex, Anticancer Res. 26, 899–904 (2006).
Q. Zhan, Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage, Mutat. Res. 569, 133–143 (2005).
A. R. Hartman and J. M. Ford, BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair, Nat. Genet. 32, 180–184 (2002).
A. R. Venkitaraman, Cancer susceptibility and the functions of BRCA1 and BRCA2, Cell 108, 171–182 (2002).
D. Ford, D. F. Easton, M. Stratton, et al., Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium, Am. J. Hum. Genet. 62, 676–689 (1998).
M. Fenech, The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations, Mutat. Res. 285, 35–44 (1993).
J. R. Meunier, A. Sarasin, and L. Marrot, Photogenotoxicity of mammalian cells: a review of the different assays for in vitro testing, Photochem. Photobiol. 75, 437–447 (2002).
G. Emri, D. Schaefer, B. Held, et al., Low concentrations of formaldehyde induce DNA damage and delay DNA repair after UV irradiation in human skin cells, Exp. Dermatol. 13, 305–315 (2004).
M. Fenech, The in vitro micronucleus technique, Mutat. Res. 455, 81–95 (2000).
T. S. Rafferty, R. C. McKenzie, J. A. Hunter, et al., Differential expression of selenoproteins by human skin cells and protection by selenium from UVB-radiation-induced cell death, Biochem. J. 332(Pt. 1), 231–236 (1998).
R. D. Snyder, Effects of sodium selenite on DNA and carcinogen-induced DNA repair in human diploid fibroblasts, Cancer Lett. 34, 73–81 (1987).
T. S. Rafferty, M. H. Green, J. E. Lowe, et al., Effects of selenium compounds on induction of DNA damage by broadband ultraviolet radiation in human keratinocytes, Br. J. Dermatol. 148, 1001–1009 (2003).
T. S. Rafferty, G. J. Beckett, C. Walker, Y. C. Bissett, and R. C. McKenzie, Selenium protects primary human keratinocytes from apoptosis induced by exposure to ultraviolet radiation, Clin. Exp. Dermatol. 28, 294–300 (2003).
B. C. Pence, E. Delver, and D. M. Dunn, Effects of dietary selenium on UVB-induced skin carcinogenesis and epidermal antioxidant status, J. Invest. Dermatol. 102, 759–761 (1994).
T. M. Cao, F. Y. Hua, C. M. Xu, et al., Distinct effects of different concentrations of sodium selenite on apoptosis, cell cycle, and gene expression profile in acute promyeloytic leukemia-derived NB4 cells, Ann. Hematol. 85, 434–442 (2006).
D. Hatfield, B. J. Lee, L. Hampton, and A. M. Diamond, Selenium induces changes in the selenocysteine tRNA(Ser)Sec population in mammalian cells, Nucleic Acids Res. 19, 939–943 (1991).
A. M. Diamond, I. S. Choi, P. F. Crain, et al., Dietary selenium affects methylation of the wobble nucleoside in the anticodon of selenocysteine tRNA(Ser)Sec. J. Biol. Chem. 268, 14,215–14,223 (1993).
H. J. Baek, H. S. Chittum, E. S. Yaung, et al., Response of the selenocysteine tRNA population to selenium in mammals and Xenopus oocytes, Nucleic Acids Symp. Ser. 36, 157–158 (1997).
M. E. Moustafa, B. A. Carlson, M. A. El-Saadani, et al., Selective inhibition of selenocysteine tRNA maturation and selenoprotein synthesis in transgenic mice expressing isopentenyladenosine-deficient selenocysteine tRNA, Mol. Cell. Biol. 21, 3840–3852 (2001).
R. R. Jameson and A. M. Diamond, A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis, RNA 10, 1142–1152 (2004).
V. Diwadkar-Navsariwala and A. M. Diamond, The link between selenium and chemoprevention: a case for selenoproteins, J. Nutr. 134, 2899–2902 (2004).
J. Liu, M. M. Hinkhouse, W. Sun, et al., Redox regulation of pancreatic cancer cell growth: role of glutathione peroxidase in the suppression of the malignant phenotype, Hum. Gene. Ther. 15, 239–250 (2004).
E. Kumaraswamy, B. A. Carlson, F. Morgan, et al., Selective removal of the selenocysteine tRNA [Ser]Sec gene (Trsp) in mouse mammary epithelium, Mol. Cell. Biol. 23, 1477–1488 (2003).
M. A. Nasr, M. J. Fedele, K. Esser, and A. M. Diamond, GPx-1 modulates Akt and P70(S6K) phosphorylation and Gadd45 levels in MCF-7 cells, Free. Radical. Biol. Med. 37, 187–195 (2004).
E. Kowalska, S. A. Narod, T. Huzarski, et al., Increased rates of chromosome breakage in BRCA1 carriers are normalized by oral selenium supplementation, Cancer Epidemiol. Biomarkers Prev. 14, 1302–1306 (2005).
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Baliga, M.S., Wang, H., Zhuo, P. et al. Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage. Biol Trace Elem Res 115, 227–241 (2007). https://doi.org/10.1007/BF02685998
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DOI: https://doi.org/10.1007/BF02685998