title: Indirect mechanism of lead-induced genotoxicity in cultured mammalian cells.
abstract: The data concerning the mutagenic, clastogenic and carcinogenic properties of inorganic lead compounds have been conflicting. To investigate whether the genotoxicity of lead is due to indirect effects such as interference with DNA-repair processes, the induction of mutations, sister-chromatid exchanges and strand breaks by lead ions alone as well as in combination with UV light as a standard mutagen were determined. Lead acetate alone does not induce DNA-strand breaks in HeLa cells or mutations at the HPRT locus and sister-chromatid exchanges in V79 Chinese hamster cells. However, at all endpoints tested, lead ions interfere with the processing of UV-induced DNA damage. They inhibit the closing of DNA-strand breaks after UV irradiation and enhance the number of UV-induced mutations and sister-chromatid exchanges, indicating an inhibition of DNA repair. These data point out the necessity to consider such indirect effects when assessing the genotoxicity of metal compounds. As possible mechanisms of repair inhibition we suggest either the interaction with repair enzymes such as polymerase or ligase or else the interaction with calcium-regulated processes, for example with calmodulin.
authors.affiliation: Department of Biology and Chemistry, University of Bremen, F.R.G.
authors.forename: A
authors.initials: A
authors.lastname: Hartwig
authors.forename: R
authors.initials: R
authors.lastname: Schlepegrell
authors.forename: D
authors.initials: D
authors.lastname: Beyersmann
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D009154:Mutation; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D007854:Lead