Skip to main content
Log in

Selenium and GPx-1 overexpression protect mammalian cells against UV-induced DNA damage

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. 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).

    Google Scholar 

  2. D. L. Hatfield and V. N. Gladyshev, How selenium has altered our understanding of the genetic code, Mol. Cell. Biol. 22, 3565–3576 (2002).

    Article  PubMed  CAS  Google Scholar 

  3. G. V. Kryukov, S. Castellano, S. V. Novoselov, et al., Characterization of mammalian selenoproteomes, Science 300, 1439–1443 (2003).

    Article  PubMed  CAS  Google Scholar 

  4. 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).

    PubMed  CAS  Google Scholar 

  5. 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).

    Article  PubMed  CAS  Google Scholar 

  6. 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).

    Article  PubMed  CAS  Google Scholar 

  7. 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).

    PubMed  CAS  Google Scholar 

  8. 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).

    Article  CAS  Google Scholar 

  9. 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).

    PubMed  CAS  Google Scholar 

  10. 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).

    Article  PubMed  CAS  Google Scholar 

  11. 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).

    PubMed  Google Scholar 

  12. Y. R. Seo, C. Sweeney, and M. L. Smith, Selenomethionine induction of DNA repair response in human fibroblasts, Oncogene 21, 3663–3669 (2002).

    Article  PubMed  CAS  Google Scholar 

  13. 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).

    Article  PubMed  CAS  Google Scholar 

  14. 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).

    PubMed  CAS  Google Scholar 

  15. M. Fenech and A. A. Morley, Measurement of micronuclei in lymphocytes, Mutat. Res. 147, 29–36 (1985).

    PubMed  CAS  Google Scholar 

  16. 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).

    PubMed  CAS  Google Scholar 

  17. Q. Zhan, Gadd45a, a p53- and BRCA1-regulated stress protein, in cellular response to DNA damage, Mutat. Res. 569, 133–143 (2005).

    PubMed  CAS  Google Scholar 

  18. A. R. Hartman and J. M. Ford, BRCA1 induces DNA damage recognition factors and enhances nucleotide excision repair, Nat. Genet. 32, 180–184 (2002).

    Article  PubMed  CAS  Google Scholar 

  19. A. R. Venkitaraman, Cancer susceptibility and the functions of BRCA1 and BRCA2, Cell 108, 171–182 (2002).

    Article  PubMed  CAS  Google Scholar 

  20. 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).

    Article  PubMed  CAS  Google Scholar 

  21. 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).

    PubMed  CAS  Google Scholar 

  22. 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).

    Article  PubMed  CAS  Google Scholar 

  23. 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).

    Article  PubMed  CAS  Google Scholar 

  24. M. Fenech, The in vitro micronucleus technique, Mutat. Res. 455, 81–95 (2000).

    PubMed  CAS  Google Scholar 

  25. 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).

    PubMed  CAS  Google Scholar 

  26. R. D. Snyder, Effects of sodium selenite on DNA and carcinogen-induced DNA repair in human diploid fibroblasts, Cancer Lett. 34, 73–81 (1987).

    Article  PubMed  CAS  Google Scholar 

  27. 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).

    Article  PubMed  CAS  Google Scholar 

  28. 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).

    Article  PubMed  CAS  Google Scholar 

  29. 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).

    Article  PubMed  CAS  Google Scholar 

  30. 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).

    Article  PubMed  CAS  Google Scholar 

  31. 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).

    Article  PubMed  CAS  Google Scholar 

  32. 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).

    CAS  Google Scholar 

  33. 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).

    CAS  Google Scholar 

  34. 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).

    Article  PubMed  CAS  Google Scholar 

  35. R. R. Jameson and A. M. Diamond, A regulatory role for Sec tRNA[Ser]Sec in selenoprotein synthesis, RNA 10, 1142–1152 (2004).

    Article  PubMed  CAS  Google Scholar 

  36. V. Diwadkar-Navsariwala and A. M. Diamond, The link between selenium and chemoprevention: a case for selenoproteins, J. Nutr. 134, 2899–2902 (2004).

    PubMed  CAS  Google Scholar 

  37. 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).

    Article  PubMed  CAS  Google Scholar 

  38. 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).

    Article  PubMed  CAS  Google Scholar 

  39. 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).

    Article  CAS  Google Scholar 

  40. 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).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02685998

Index Entries

Navigation