Effect of fludarabine on leukocyte functions.
BACKGROUND
Fludarabine induces leukemic cell apoptosis and is highly efficient in chronic lymphocytic leukemia. However, fludarabine therapy causes severe leukopenia. Leukocyte myeloperoxidase (MPO) catalyzes the formation of HOCl, and this is the main microbicidal function in phagocytes. The aim of our study was to evaluate the effect of fludarabine on leukocytes, i.e. their degranulation capacity, MPO activity and HOCl production.


METHODS
Peripheral blood leukocytes were incubated for 48 h with fludarabine. Degranulation was measured using a flow-cytometric method. MPO activity and HOCl production were measured spectrophotometrically.


RESULTS
The degranulation capacity of fludarabine-treated leukocytes was significantly elevated compared to untreated controls. MPO activity and HOCl production were also increased in parallel. A possible direct activating effect of fludarabine was tested on the MPO activity of HL60 cells. Fludarabine did not affect MPO activity at concentrations ranging from 10 microM to 2 mM.


CONCLUSIONS
Fludarabine had no inhibitory effect on the microbial killing of leukocytes.
Doğan
A Lale
AL
Department of Basic Oncology, Institute of Oncology, Hacettepe University, Ankara, Turkey.
Doğan
Ayça
A
Canpinar
Hande
H
Duzgunçinar
Ovunç
O
Demirpençe
Ediz
E
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000379:methods; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D014740:Vidarabine / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D006997:Hypochlorous Acid; D009195:Peroxidase; D014740:Vidarabine; C024352:fludarabine