Differential toxicity of cytosine arabinoside to cell kinetics in normal sheep sinus cells and sheep tumour cell line in vitro.
The effects of 1-beta-d-arabinofuranosylcytosine (ara-c) on cell proliferation, morphology and cycle progression were compared in a sheep tumour cell line and normal sheep sinus cells. The effects were found to be dose and time dependent and reversible, and were accompanied by increased cell size and cytosolic synthetic activities. Ara-c induced a concentration-dependent inhibition of cell proliferation in both normal and tumour cells. However, normal cells were less sensitive than tumour cells when exposed to a low concentration of ara-c (10(-6)m). The two cell types exhibited equal sensitivity to higher drug concentrations (10(-5) and 10(-4)m). Flow cytometric analysis (FCM) of cell cycle progression and right-angle scatter using these two cell types confirmed that a concentration of 10(-6)m-ara-c had little or no effect on normal cells while tumour cells showed increases in size and accumulation in the S phase. These findings may provide new insights into how ara-c cytotoxicity may be reduced or avoided in normal tissue provided that tumour cells are selectively affected by low-dose ara-c in vivo.
Shrivastava
R S
RS
Service Universitaire de Cytofluorométrie, Faculté de Médecine, 87025, Limoges, France.
Ratinaud
M H
MH
Julien
R
R