title: Induction of DNA double-strand breaks in the H4IIE cell line exposed to environmentally relevant concentrations of copper, cadmium, and zinc, singly and in combinations.
abstract: Xenobiotics, including heavy metals, exist in nature as complex mixtures of compounds with possible interactions. Induction of DNA damage such as DNA strand breaks may exert detrimental consequences to both individuals and populations. In this study, the induction of DNA double-strand breaks was assessed using the H4IIE rat hepatoma cell line following exposure to high and environmentally relevant concentrations of chloride salts of the metals cadmium (Cd), copper (Cu), and zinc (Zn), both singly and in combination. DNA strand break analysis was performed using agarose gel electrophoresis. Median molecular lengths were calculated from fragment size distributions acquired from gel image data and were used as a quantitative measure of DNA double-strand break induction. Exposure to high concentrations of Cu and Cd in combination produced a significant increase in the occurrence of DNA strand break. However, exposing cells to high concentrations of Cu, Cd, and Zn in combination resulted in significantly lower DNA double-strand break compared to control cells. Addition of low Zn to the Cd/Cu mixture restored DNA damage level back to that of the control. Environmentally relevant concentrations of Cd, Cu, and Zn did not appear to induce DNA strand breaks in the H4IIE cell line.
authors.affiliation: Department of Biology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Renate
authors.initials: R
authors.lastname: Haldsrud
authors.forename: Ase
authors.initials: A
authors.lastname: Krøkje
mesh_terms: D000818:Animals; D002104:Cadmium / Q000032:analysis / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000032:analysis / Q000633:toxicity; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004587:Electrophoresis, Agar Gel; D004785:Environmental Pollutants / Q000633:toxicity; D005562:Formazans / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D019216:Metals, Heavy / Q000032:analysis / Q000633:toxicity*; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*; D015032:Zinc / Q000032:analysis / Q000633:toxicity
chemical_list: D004273:DNA, Neoplasm; D004338:Drug Combinations; D004785:Environmental Pollutants; D005562:Formazans; D019216:Metals, Heavy; D013778:Tetrazolium Salts; D014874:Water Pollutants, Chemical; D002104:Cadmium; C079782:MTT formazan; D003300:Copper; D015032:Zinc