title: DNA damage and oxidative stress response to selenium yeast in the non-smoking individuals: a short-term supplementation trial with respect to GPX1 and SEPP1 polymorphism.
abstract: OBJECTIVE
  Selenium, both essential and toxic element, is considered to protect against cancer, though human supplementation trials have generated many inconsistent data. Genetic background may partially explain a great variability of the studies related to selenium and human health. The aim of this study was to assess whether functional polymorphisms within two selenoprotein-encoding genes modify the response to selenium at the level of oxidative stress, DNA damage, and mRNA expression, especially in the individuals with a relatively low selenium status.
  
  
  METHODS
  The trial involved 95 non-smoking individuals, stratified according to GPX1 rs1050450 and SEPP1 rs3877899 genotypes, and supplemented with selenium yeast (200 µg) for 6 weeks. Blood was collected at four time points, including 4 weeks of washout.
  
  
  RESULTS
  After genotype stratification, the effect of GPX1 rs1050450 on lower GPx1 activity responsiveness was confirmed; however, in terms of DNA damage, we failed to indicate that individuals homozygous for variant allele may especially benefit from the increased selenium intake. Surprisingly, considering gene and time interaction, GPX1 polymorphism was observed to modify the level of DNA strand breaks during washout, showing a significant increase in GPX1 wild-type homozygotes. Regardless of the genotype, selenium supplementation was associated with a selectively suppressed selenoprotein mRNA expression and inconsistent changes in oxidative stress response, indicating for overlapped, antioxidant, and prooxidant effects. Intriguingly, DNA damage was not influenced by supplementation, but it was significantly increased during washout.
  
  
  CONCLUSIONS
  These results point to an unclear relationship between selenium, genotype, and DNA damage.
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland. ewa@imp.lodz.pl.
authors.forename: E
authors.initials: E
authors.lastname: Jablonska
authors.affiliation: Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Raimondi
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Gromadzinska
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Reszka
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Wieczorek
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: M B
authors.initials: MB
authors.lastname: Krol
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Smok-Pieniazek
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Nocun
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Stepnik
authors.affiliation: Department of Bromatology, Medical University of Bialystok, Mickiewicza 2D Street, 15-222, Białystok, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Socha
authors.affiliation: Department of Bromatology, Medical University of Bialystok, Mickiewicza 2D Street, 15-222, Białystok, Poland.
authors.forename: M H
authors.initials: MH
authors.lastname: Borawska
authors.affiliation: Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, St. Teresy 8 Street, 91-348, Lodz, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wasowicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D004249:DNA Damage / Q000187:drug effects*; D019587:Dietary Supplements; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques; D005979:Glutathione Peroxidase / Q000097:blood / Q000235:genetics*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D012643:Selenium / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D051140:Selenoproteins / Q000097:blood / Q000235:genetics*; D055815:Young Adult; D000094765:Glutathione Peroxidase GPX1
chemical_list: D012333:RNA, Messenger; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1
keywords: DNA damage; Gene expression; Oxidative stress; Selenium; Selenium supplementation; Selenoproteins