Amifostine differentially modulates DNA damage evoked by idarubicin in normal and leukemic cells.
Human lymphocytes, p53 protein-deficient acute promyelocytic leukemia cell line HL-60, murine pro-B lymphoid cell line BaF3 and its TEL/ABL-transformed clone cells were exposed to idarubicin with and without pre-treatment with amifostine. Idarubicin at 0.5-5 microM evoked DNA damage measured by the Comet assay. Amifostine at 14 mM decreased DNA-damaging effect of idarubicin in human lymphocytes and BaF3 cells, but increased the effect in TEL/ABL-transformed cells. Amifostine had no influence on the action of idarubicin in HL-60 cells. Our results suggest that the reaction of the cell to DNA damage may contribute to its diverse response to amifostine combined with anticancer drugs and that p53 and fusion tyrosine kinases may be involved in this diversity.
Błasiak
Janusz
J
Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland. januszb@biol.uni.lodz.pl
Gloc
Ewa
E
Młynarski
Wojciech
W
Drzewoski
Józef
J
Skórski
Tomasz
T
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; D014407:Tumor Cells, Cultured; D000097764:ETS Translocation Variant 6 Protein
D004999:Amifostine; D015255:Idarubicin; D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C426234:TEL-ABL fusion protein, human; D000097764:ETS Translocation Variant 6 Protein