title: In vitro effects of simultaneous exposure to platinum and cadmium on the activity of antioxidant enzymes and DNA damage and potential protective effects of selenium and zinc.
abstract: Circulating platinum (Pt) is detectable in the blood of Pt-treated cancer patients for over a decade after the treatment. Prolonged exposure to Pt, in combination with adverse compounds from nutrition and lifestyle, such as cadmium (Cd), could increase the risk from second cancers. The aim of this study was to investigate the effects of simultaneous exposure to Cd- and Pt-compounds on oxidative and DNA damage and the possible protective effects of zinc (Zn) and selenium (Se). The aqueous solutions of PtCl4, CdCl2×H2O, ZnCl2and Na2SeO3were added, alone or in combination, to whole blood and isolated erythrocytes to produce the final concentrations of 2000 μg/L of Pt, 8 μg/L of Cd, 100 μg/L of Se, and 1000 μg/L of Zn. The activity of copper, zinc-superoxide dismutase, glutathione peroxidase and glutathione in whole blood was determined after 1 h exposure in in vitro conditions. The induction of DNA strand-breaks in human peripheral blood leukocytes was determined with the alkaline comet assay after 24 h exposure. Exposure to Pt and/or Cd decreased the activities of antioxidant enzymes and elevated DNA damage compared to control. A statistically significant change in the activity of both enzymes and in the induction of DNA strand-breaks was observed in the cells treated with Pt + Cd combination, while the addition of Se and/or Zn resulted in partial recovery of these effects. The results indicate that combined exposure to Pt and Cd could disrupt antioxidant protection of the organism and increase DNA damage, whereas Se and Zn could partially ameliorate these harmful effects.
authors.affiliation: a Analytical Toxicology and Mineral Metabolism Unit.
authors.forename: Blanka
authors.initials: B
authors.lastname: Tariba
authors.affiliation: a Analytical Toxicology and Mineral Metabolism Unit.
authors.forename: Tanja
authors.initials: T
authors.lastname: Živković
authors.affiliation: b Mutagenesis Unit , and.
authors.forename: Goran
authors.initials: G
authors.lastname: Gajski
authors.affiliation: b Mutagenesis Unit , and.
authors.forename: Marko
authors.initials: M
authors.lastname: Gerić
authors.affiliation: c Unit of Toxicology, Institute for Medical Research and Occupational Health , Zagreb , Croatia.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gluščić
authors.affiliation: b Mutagenesis Unit , and.
authors.forename: Vera
authors.initials: V
authors.lastname: Garaj-Vrhovac
authors.affiliation: c Unit of Toxicology, Institute for Medical Research and Occupational Health , Zagreb , Croatia.
authors.forename: Maja
authors.initials: M
authors.lastname: Peraica
authors.affiliation: a Analytical Toxicology and Mineral Metabolism Unit.
authors.forename: Alica
authors.initials: A
authors.lastname: Pizent
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D019256:Cadmium Chloride / Q000633:toxicity*; D002712:Chlorides / Q000494:pharmacology*; D020552:Comet Assay; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects*; D004798:Enzymes / Q000097:blood*; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017671:Platinum Compounds / Q000633:toxicity*; D018038:Sodium Selenite / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000097:blood; D055815:Young Adult; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002712:Chlorides; D004798:Enzymes; D009153:Mutagens; D017671:Platinum Compounds; D017967:Zinc Compounds; C030173:platinum chloride; C016837:zinc chloride; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D018038:Sodium Selenite; D019256:Cadmium Chloride
keywords: Glutathione peroxidase; cadmium; chemotherapy; essential elements; platinum; superoxide dismutase