Effect of ERCC-1 overexpression on sensitivity of Chinese hamster ovary cells to DNA damaging agents.
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Previous studies of ERCC-1 gene expression levels in chronic lymphocytic leukemia and ovarian carcinoma tumor specimens indicated that increased gene expression may correlate with a lack of response to the alkylating agents, melphalan, and cis-diamminedichloroplatinum (II). In order to demonstrate direct involvement of the ERCC-1 protein in repair of melphalan lesions, the ERCC-1 defective Chinese hamster ovary cell line UV20 was transfected with the human ERCC-1 complementary DNA. Stably transfected UV20 cells demonstrated an increase in resistance to melphalan. Wild type Chinese hamster ovary AA8 cells were then stably transfected with the same complementary DNA. The result was an increase in sensitivity to melphalan. There was no effect on sensitivity to uv light, but the ERCC-1 transfected AA8 cells had an increased sensitivity to cis-diamminedichloroplatinum (II). These results suggest that overexpression of human ERCC-1 may inhibit a pathway specific to the repair of bifunctional DNA damaging agent lesions in AA8 cells. ERCC-1 transfected AA8 cells should be useful in determining the precise role of ERCC-1 in repair of DNA cross-links induced by melphalan.
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