Discrepancy of Cadmium Susceptibility Between Human RSa Cells and Variant UVr-1 Cells

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It is important to search for mechanisms which suppress the mutagenicity of environmental agents in human cells and to utilize cultured human cells which are suitable for this search. In this study a human RSa cell line was used for the detection of cadmium mutagenicity. RSa cells were already found to be hypermutable after treatment with various agents, as assessed by both phenotypic and genetic mutation tests, ouabain-resistance (OuaR) tests and differential dot-blot hybridization tests. Treatment of RSa cells with cadmium resulted in a 1.97 fold increase in the frequency of OuaR mutation in comparison with the frequency with mock treatment. In contrast, UVr-1 cells derived from RSa cells as a UV-resistant variant cells, showed slightly increase of OuaR mutation frequency after cadmium treatment. Moreover, K-ras codon 12 mutations in genomic DNA from cadmium-treated RSa cells were detected by polymerase chain reaction following differential dot blot hybridization, whereas the mutation was not detected in UVr-1 cells. DNA damage, which was detected by comet assay, was detected after cadmium treatment in both RSa and UVr-1 cells. There is no difference of excision repair capacity between RSa and UVr-1 cells. Thus, RSa cells are hypermutable for cadmium and DNA repair but for excision repair may be related with the hypermutability.

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