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Selenium and GPx‐1 affect H2AX phosphorylation and cell survival
Author(s) -
JeromeMorais Anita,
Diamond Alan M.
Publication year - 2011
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.25.1_supplement.110.2
Subject(s) - glutathione peroxidase , gpx1 , selenoprotein , dna damage , cancer research , chemistry , microbiology and biotechnology , biology , endocrinology , biochemistry , superoxide dismutase , oxidative stress , dna
Selenium (Se) reduces cancer incidence in animals and there is an inverse association between Se intake and risk of certain cancers. The glutathione peroxidase‐1 (GPx‐1) selenoprotein has been implicated in cancer etiology based on its anti‐oxidant activity, ability to protect cells from DNA damage in vitro and by human genetics. To gain an understanding of the effects of Se and GPx‐1 on the DNA damage response, human HCT116 colon carcinoma cells and NCM460 immortalized colon epithelial cells were exposed to 4 Gy of X‐rays and phosphorylation of histone H2AX, a marker of DNA damage, was evaluated by flow cytometry with or without media supplementation of 30 nM selenite. Se supplementation increased GPx activity in both cell types and significantly increased the turnover of radiation induced P~H2AX in HCT116 cells; this did not occur NCM460. Addition of Se protected HCT116 but not NCM460 from radiation induced toxicity determined using MTT. To evaluate the effects of GPx‐1 in the response to X‐ray exposure, MCF7 breast cancer cells that express negligible levels of GPx‐1 were compared to MCF7 that express GPx‐1 due to transfection. GPx over‐expression resulted in increased P~H2AX levels. Se supplementation protected MCF7‐GPx cells but not control MCF7 from radiation toxicity. Se and GPx1 may enhance DNA repair, accounting for some of Se's benefits. This work is supported by NIH grant 1RO1CA127943 to AM Diamond.