Influence of 2-chlorodeoxyadenosine (cladribine) on human erythrocytes.
2-Chlorodeoxyadenosine (2-CdA, cladribine) is one of the newest chemotherapy drugs which has been around and in use for a few years. Drug in tumour cells causes the inhibition of DNA synthesis and repair processes in replication cells, and the accumulation of DNA strand breaks in nonproliferating cells. The present study was undertaken to characterize the influence of cladribine on the fluidity of the lipid bilayer and protein conformation in human erythrocytes. The effect of cladribine on the erythrocyte membrane structure was examined by electron spin resonance (ESR) spectroscopy and fluorescence measurements. It was observed that under the studied conditions (c: 0.1-5 microg/ml, t = 1 h, 37 degrees C), cladribine localised mainly in the erythrocyte membrane and affected its organization. The alterations in the fluidity were observed mainly in the deeper regions of the cell membrane. The incorporation of drug into human erythrocytes also caused negligible conformational alterations of membrane cytoskeletal proteins and did not change the internal viscosity of the cells. We can conclude from these data that 2-CdA in vitro is significantly much less toxic to erythrocytes than anthracycline drugs, which are used in treatment of leukemias. However, the higher concentrations of 2-CdA (about 5 microg/ml) can be also toxic to erythrocytes.
Marczak
A
A
Department of Thermobiology, University of Łødź, Poland. aszwar@biol.uni.lodz.pl
Łubgan
D
D
Robak
T
T
Jóźwiak
Z
Z
D017338:Cladribine / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects; D008565:Membrane Proteins / Q000737:chemistry; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence
D008565:Membrane Proteins; D017338:Cladribine