Effects of variation in glutathione peroxidase activity on DNA damage and cell survival in human cells exposed to hydrogen peroxide and t-butyl hydroperoxide.
The selenium-dependent glutathione peroxidase activities of two human cell lines, the colon carcinoma HT29 and the mesothelioma P31, cultured in medium containing 2% serum, increased from 195 to 541 and from 94 to 361 units/mg of protein respectively after supplementation with 100 nM-selenite. The catalase activity remained unchanged by this treatment. The effects of the obtained variation in glutathione peroxidase activities were investigated by exposing cells to H2O2 and t-butyl hydroperoxide. Selenite supplementation resulted in a decrease in H2O2-induced DNA single-strand breaks in both HT29 and P31 cells. A small, but significant, decrease in the number of DNA single-strand breaks for low doses (10-50 microM) of t-butyl hydroperoxide was found only in P31 cells and not in HT29 cells. We could detect neither induction of double-strand breaks (detection limit approx. 1000 breaks per cell) nor DNA-protein cross-links after exposing the cells to the two peroxides. In spite of the apparent protective effect of increased glutathione peroxidase activity on DNA single-strand break formation, there were no differences between selenite-supplemented and non-supplemented cells in cell survival after exposure to peroxide.
Sandström
B E
BE
Division of Ionizing Radiation and Fallout, National Defence Research Establishment, Umeå, Sweden.
Marklund
S L
SL
D002374:Catalase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008654:Mesothelioma; D010545:Peroxides / Q000494:pharmacology*; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D020122:tert-Butylhydroperoxide
D010545:Peroxides; D004247:DNA; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D020887:Selenious Acid; D012643:Selenium