title: Does the bcr/abl-mediated increase in the efficacy of DNA repair play a role in the drug resistance of cancer cells?
abstract: BCR/ABL oncogenic tyrosine kinase is responsible for the pathogenesis of Philadelphia chromosome-positive human leukemia and is generated by a specific reciprocal chromosome translocation, t(9;22)(q34-;q11+). We examined the role of DNA repair in therapeutic drug resistance to idarubicin in the murine pro-B lymphoid cell line BaF3 and its BCR/ABL -transformed clone. These cells can be used as models of human leukemias. The MTT assay revealed that BCR/ABL -transformed cells displayed resistance to idarubicin in the range 0.3-0.5 microm, compared with the control BaF3 cells. Idarubicin at 0.3 and 1 microm induced DNA damage in the form of strand-breaks and/or alkali labile sites in both transformed and control cells in comet assays. The BCR/ABL -transformed cells needed only 60 min to remove damage to their DNA, whereas controls took 120 min. We hypothesize that this observed increase in the efficacy of repair in BCR/ABL- positive cells is involved in their resistance to idarubicin.
authors: Department of Molecular Genetics, University of Lodz, Poland.
authors: Ireneusz
authors: I
authors: Majsterek
authors: Janusz
authors: J
authors: Blasiak
authors: Wojciech
authors: W
authors: Mlynarski
authors: Grazyna
authors: G
authors: Hoser
authors: Tomasz
authors: T
authors: Skórski
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D020552:Comet Assay; D004260:DNA Repair / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D016313:Genes, abl; D015255:Idarubicin / Q000494:pharmacology; D008214:Lymphocytes; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000235:genetics
chemical_list: D000903:Antibiotics, Antineoplastic; D016044:Fusion Proteins, bcr-abl; D015255:Idarubicin