title: Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate.
abstract: Lead, an environmental toxin is known to induce a broad range of physiological and biochemical dysfunctions in humans through a number of mechanisms including the deactivation of antioxidants thus leading to generation of reactive oxygen species (ROS) and subsequent DNA damage. Selenium on the other hand has been proven to play an important role in the protection of cells from free radical damage and oxidative stress, though its effects are thought to be form and dose dependent. As the liver is the primary organ required for metabolite detoxification, HepG2 cells were chosen to assess the protective effects of various selenium compounds following exposure to the genotoxic agent lead nitrate. Initially DNA damage was quantified using a comet assay, gene expression patterns associated with DNA damage and signalling were also examined using PCR arrays and the biological pathways which were most significantly affected by selenium were identified. Interestingly, the organic type selenium compounds (selenium yeast and selenomethionine) conferred protection against lead induced DNA damage in HepG2 cells; this is evident by reduction in the quantity of DNA present in the comet tail of cells cultured in their presence with lead. This trend also followed through the gene expression changes noted in DNA damage pathways analysed. These results were in contrast with those of inorganic sodium selenite which promoted lead induced DNA damage evident in both the comet assay results and the gene expression analysis. Over all this study provided valuable insights into the effects which various selenium compounds had on the DNA damage and signalling pathway indicating the potential for using organic forms of selenium such as selenium enriched yeast to protect against DNA damaging agents.
authors.affiliation: Alltech Biotechnology Centre, Sarney, Summerhill Rd., Dunboyne, County Meath, Ireland. Electronic address: smckelvey@alltech.com.
authors.forename: Shauna M
authors.initials: SM
authors.lastname: McKelvey
authors.affiliation: Alltech Biotechnology Centre, Sarney, Summerhill Rd., Dunboyne, County Meath, Ireland.
authors.forename: Karina A
authors.initials: KA
authors.lastname: Horgan
authors.affiliation: Alltech Biotechnology Centre, Sarney, Summerhill Rd., Dunboyne, County Meath, Ireland.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Murphy
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007854:Lead / Q000633:toxicity*; D008954:Models, Biological; D009566:Nitrates / Q000633:toxicity*; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D009566:Nitrates; D007854:Lead; C017461:lead nitrate; D012643:Selenium
keywords: Comet assay; DNA repair pathways; Gene expression; Lead; Selenium