Deferasirox-induced cytogenetic responses.
Deferasirox (commercially formulated as Exjade(®)) is one of the effective iron chelators used in treatment of iron overload diseases. In this study the effect of this substance for chromosome aberration, sister chromatid exchange and mitotic index was studied by in vitro (by using human peripheral lymphocytes) and in vivo (by using rat) analysis. Deferasirox increased the sister chromatid exchange frequency in all tested concentrations and periods in vitro. Also, in the presence of metabolic activator, the substance led to a statistically significant increase in the sister chromatid exchange frequencies only at high concentration. While in in vitro analysis the substance significantly increased abnormal cell percentages in all concentrations, in in vivo study the substance increased chromosome aberrations only in two concentrations at 12h treatment. In the cultured lymphocytes, deferasirox showed cytotoxicity by significantly reducing proliferation index and mitotic index values. While in the presence of metabolic activation it did not affect the proliferation index frequency, it had a stimulant effect on the mitotic index frequency. Deferasirox reduced significantly the mitotic index value in the bone marrow cells especially in high concentration and short treatment period (12h).
Ardahan University, School of Health Sciences, Department of Nursing, 75000 Ardahan, Turkey. Electronic address: mehmetarslan@ardahan.edu.tr.
Mehmet
M
Arslan
Cukurova University, Faculty of Science and Letters, Department of Biology, 01330 Adana, Turkey.
Hasan Basri
HB
Ila
D000328:Adult; D000818:Animals; D001565:Benzoates / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced; D000077588:Deferasirox; D005260:Female; D006801:Humans; D007502:Iron Chelating Agents / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D012854:Sister Chromatid Exchange / Q000187:drug effects; D014230:Triazoles / Q000633:toxicity*; D055815:Young Adult
D001565:Benzoates; D007502:Iron Chelating Agents; D009153:Mutagens; D014230:Triazoles; D000077588:Deferasirox
Cytotoxicity; Deferasirox; Genotoxicity; In vitro; In vivo; Iron chelator