Modulation by Co(II) of UV-induced DNA repair, mutagenesis and sister-chromatid exchanges in mammalian cells.
In bacterial test systems, Co(II) has been shown to be antimutagenic in combination with several chemical and physical agents. To investigate whether such modulations also apply to mammalian cells, the effect of Co(II) on UV-induced mutagenesis, sister-chromatid exchanges as well as DNA damage and its removal was determined. Co(II) itself is weakly mutagenic at the HPRT locus and increases the frequency of sister-chromatid exchanges. Additionally, at both endpoints the metal ions enhance the genotoxicity of UV light. To discriminate between an enhancement of DNA damage and an interference with repair processes, the number of pyrimidine cyclobutane dimers was determined by HPLC. While the induction of these DNA lesions is not affected by Co(II), their removal is inhibited at concentrations of 75 microM Co(II) and higher. Analysis of the kinetics of strand-break induction and closure after UV irradiation by nucleoid sedimentation reveals an accumulation of strand breaks in the presence of Co(II). This indicates that either the polymerization or the ligation step in excision repair is affected. Since similar interactions with the processing of UV-induced DNA damage have been observed with other carcinogenic and/or mutagenic metal ions, this appears to be a common mechanism of metal genotoxicity.
Hartwig
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A
Department of Biology and Chemistry, University of Bremen, F.R.G.
Snyder
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RD
Schlepegrell
R
R
Beyersmann
D
D
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003035:Cobalt / Q000494:pharmacology*; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects / Q000528:radiation effects; D011740:Pyrimidine Dimers; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014466:Ultraviolet Rays / Q000009:adverse effects
D004277:DNA, Single-Stranded; D011740:Pyrimidine Dimers; D011838:Radiation-Sensitizing Agents; D003035:Cobalt