title: Interaction of carcinogenic metal compounds with deoxyribonucleic acid repair processes.
abstract: The potentials of nickel(II) and cadmium(II) to interfere with the repair of different types of deoxyribonucleic acid (DNA) lesions was investigated. Concerning the nucleotide excision repair pathway, nickel(II) has been shown to reduce the incision and the ligation frequency after ultraviolet (UV)-irradiation. When applying a gel mobility shift assay and HeLa nuclear cell free extracts, nickel(II) diminishes the specific binding of a protein to UV-damaged DNA, suggesting that nickel(II) interferes with the DNA-protein interactions involved in the damage recognition after UV-irradiation. Similarly, the incision frequency is reduced in the presence of low concentrations of cadmium(II). Concerning the repair of oxidative DNA damage induced by visible light, non-cytotoxic concentrations of nickel(II) caused a complete repair inhibition of DNA base modifications like 7,8-dihydro-8-oxoguanine (8-hydroxyguanine) and of DNA strand breaks. Since the repair of DNA damage is essential for the prevention of cancer, its inhibition may account for the carcinogenic action of the respective metal compounds.
authors.affiliation: Department of Biology and Chemistry, University of Bremen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hartwig
authors.forename: R
authors.initials: R
authors.lastname: Schlepegrell
authors.forename: H
authors.initials: H
authors.lastname: Dally
authors.forename: M
authors.initials: M
authors.lastname: Hartmann
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D002104:Cadmium / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D003035:Cobalt / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D009532:Nickel / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D002104:Cadmium; D003035:Cobalt; D009532:Nickel; D001151:Arsenic