title: Molecular and genomic approach for understanding the gene-environment             interaction between Nrf2 deficiency and carcinogenic nickel-induced DNA damage.
abstract: Nickel (Ⅱ) is a toxic and carcinogenic metal which induces a redox imbalance             following oxidative stress. Nuclear factor erythroid-2 related factor 2 (Nrf2)             is a redox factor that regulates oxidation/reduction status and consequently mediates             cytoprotective responses against exposure to environmental toxicants. In this             study, we investigated the protective roles of the Nrf2 gene against oxidative             stress and DNA damage induced by nickel at sub-lethal doses. Under nickel exposure             conditions, we detected significantly increased intracellular ROS generation,             in addition to higher amounts of DNA damage using comet assay and γ-H2AX immunofluorescence             staining in Nrf2 lacking cells, as compared to Nrf2 wild-type cells. In addition,             we attempted to identify potential nickel and Nrf2-responsive targets and the             relevant pathway. The genomic expression data were analyzed using microarray for             the selection of synergistic effect-related genes by Nrf2 knockdown under nickel             treatment. In particular, altered expressions of 6 upregulated genes (CAV1, FOSL2,             MICA, PIM2, RUNX1 and SLC7A6) and 4 downregulated genes (APLP1, CLSPN, PCAF and             PRAME) were confirmed by qRT-PCR. Additionally, using bioinformatics tool, we             found that these genes functioned principally in a variety of molecular processes,             including oxidative stress response, necrosis, DNA repair and cell survival. Thus,             we describe the potential biomarkers regarded as molecular candidates for Nrf2-related             cellular protection against nickel exposure. In conclusion, these findings indicate             that Nrf2 is an important factor with a protective role in the suppression of             mutagenicity and carcinogenicity by environmental nickel exposure in terms of             gene-environment interaction.
authors.affiliation: Department of Life Science, Dongguk University, Jung-gu, Seoul 100-715, Republic of Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Kim
authors.forename: Young Rok
authors.initials: YR
authors.lastname: Seo
mesh_terms: D000085:Acetates / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D019610:Cytoprotection; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D059647:Gene-Environment Interaction; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D009942:Organometallic Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering
chemical_list: D000085:Acetates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009942:Organometallic Compounds; D034741:RNA, Small Interfering; C119536:nickel acetate