title: Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCaP prostate cancer cells.
abstract: Epidemiological studies have demonstrated an inverse relationship between selenium (Se) intake and cancer incidence and/or mortality. However, the molecular mechanisms underlying the cancer chemopreventive activity of Se compounds remain largely unknown. The objective of this study was to investigate the effect of low doses of Se on the stimulation of DNA repair systems in response to four different qualities of DNA damage. P53-proficient LNCaP human prostate adenocarcinoma cells were grown either untreated or in the presence of low concentrations of two Se compounds (30° nM sodium selenite, or 10 μM selenomethionine) and exposed to UVA, H2O2, methylmethane sulfonate (MMS) or UVC. Cell viability as well as DNA damage induction and repair were evaluated by the alkaline Comet assay. Overall, Se was shown to be a very potent protector against cell toxicity and genotoxicity induced by oxidative stress (UVA or H2O2) but not from the agents that induce other types of deleterious lesions (MMS or UVC). Furthermore, Se-treated cells exhibited increased oxidative DNA repair activity, indicating a novel mechanism of Se action. Therefore, the benefits of Se could be explained by a combination of antioxidant activity, the reduction in DNA damage and the enhancement of oxidative DNA repair capacity.
authors.affiliation: Laboratoire des Lésions des Acides Nucléiques, SCIB, UMR-E CEA/UJF-Grenoble 1, INAC, Grenoble, France.
authors.forename: Viviana
authors.initials: V
authors.lastname: de Rosa
authors.forename: Pinar
authors.initials: P
authors.lastname: Erkekoğlu
authors.forename: Anne
authors.initials: A
authors.lastname: Forestier
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Filiz
authors.initials: F
authors.lastname: Hincal
authors.forename: Alan M
authors.initials: AM
authors.lastname: Diamond
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Walid
authors.initials: W
authors.lastname: Rachidi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011471:Prostatic Neoplasms; D012645:Selenomethionine / Q000494:pharmacology*; D018038:Sodium Selenite / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D014466:Ultraviolet Rays; D000094765:Glutathione Peroxidase GPX1
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D000080242:8-Hydroxy-2'-Deoxyguanosine; D012645:Selenomethionine; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013880:Thioredoxin-Disulfide Reductase; D003849:Deoxyguanosine; D018038:Sodium Selenite; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human