Uptake and genotoxicity of micromolar concentrations of cobalt chloride in mammalian cells

Abstract

Literature data concerning the genotoxicity of cobalt salts have been conflicting. To establish appropriate incubation conditions, we conducted a series of uptake studies, before genotoxicity was determined by DNA strand break induction in HeLa cells and mutagenicity in V79 Chinese hamster cells. Co(II) is taken up by HeLa cells in a concentration‐dependent manner and is accumulated inside the cell. The uptake is preceded by a fast association step to the outer membrane, with no saturation up to 24 h. DNA strand breaks as determined by nucleoid sedimentation are induced at concentrations as low as 50μMCoCl₂. The induction is time‐dependent, showing the highest number of breaks after 4h incubation with no further increase up to 24h. CoCl₂ is mutagenic at the HPRT‐locus, enhancing the spontaneous mutation frequency 4.2‐fold at 100μ?. Besides direct interactions with DNA, the mutagenicity of CoCl₂ could also be due to a decrease in the Fidelity of DNA polymerisation.