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Selenium and over‐expression of GPx‐1 protect cultured cells against DNA damage
Author(s) -
Baliga Manjeshwar S.,
Diamond Alan M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1069-d
Subject(s) - dna damage , selenium , micronucleus test , gadd45 , genotoxicity , microbiology and biotechnology , chemistry , biology , dna , cancer research , apoptosis , toxicity , biochemistry , cell cycle , cell cycle checkpoint , organic chemistry
Both animal and human data have indicated that selenium is effective in reducing cancer incidence, although the mechanism of action remains unknown. One selenium‐containing protein, GPx‐1, has been speculated to be involved with cancer etiology. One way chemopreventive compounds can reduce cancer risk is by protecting the genome from potentially mutagenic DNA damage. Whether selenium and/or GPx‐1 could protect DNA from damage caused by exposure to UV was investigated in MCF‐7 human breast carcinoma cells. DNA damage was evaluated by microscopically scoring the number of cells containing a micronucleus, a commonly used method to assess chromosomal damage. Supplementation of the culture media with 30 nM sodium selenite for 3 days prior to exposure to UV resulted in a significant decline in the number of micronuclei, as did the over‐expression of GPx‐1 achieved following transfection. The greatest protection against UV‐induced micronuclei formation was achieved with both over‐expression of GPx‐1 and selenium supplementation. It has been previously reported that selenium and GPx‐1 can marginally induce the expression of DNA damage response gene Gadd45. By western blot analysis with anti‐Gadd45 antibodies, it was observed that there was a dramatic increase in Gadd45 only when cells were exposed to UV and when GPx‐1 was over‐expressed, and this response was stimulated to a greater extent when selenium was added in the media. These data demonstrate the protective effects of GPx‐1 and selenium, and raise the possibility that they do so by stimulating a stress response pathway following the occurrence of DNA damage. This work was supported by grants from the NIH and DOD.