Enhanced DNA cross-link removal: the apparent mechanism of resistance in a clinically relevant melphalan-resistant human breast cancer cell line.

摘要: Resistance to the cytotoxic effects of alkylating agents is a major limitation their clinical efficacy. Although number animal and human tumor cell models have been developed study this problem, it has proven difficult achieve very high levels resistance in vitro. This consistent with recent evidence that alkylator can be overcome by dose escalations less than 10-fold. A mechanisms described, more one which may occur same model. paper describes breast cancer subline selected for 3-fold melphalan cross-resistant other alkylators only previously described resistance, enhanced removal DNA interstrand cross-linking, demonstrable. Northern blot analysis using incisional repair gene ERCC-1 cDNA demonstrated particular product not altered function these cells, so molecular characterization observed pending. Because cells are also radiation adriamycin epipodophyllotoxin, they represent clinically relevant model examine role lesions resulting from agents.