Premium
DOES THE BCR/ABL‐MEDIATED INCREASE IN THE EFFICACY OF DNA REPAIR PLAY A ROLE IN THE DRUG RESISTANCE OF CANCER CELLS?
Author(s) -
Majsterek Ireneusz,
Blasiak Janusz,
Mlynarski Wojciech,
Hoser Grazyna,
Skórski Tomasz
Publication year - 2002
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1006/cbir.2002.0865
Subject(s) - idarubicin , philadelphia chromosome , breakpoint cluster region , clone (java method) , dna damage , cancer research , comet assay , biology , chromosomal translocation , abl , microbiology and biotechnology , chemistry , dna , tyrosine kinase , genetics , myeloid leukemia , signal transduction , gene , cytarabine
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 0.3–0.5μ m , compared with the control BaF3 cells. Idarubicin at 0.3 and 1μ m 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 60min to remove damage to their DNA, whereas controls took 120min. We hypothesize that this observed increase in the efficacy of repair in BCR/ABL‐ positive cells is involved in their resistance to idarubicin.