DNA protein flow cytometry of dissociated cultures of human anaplastic gliomas. Pattern of proliferation and differentiation, and the effect of a new cytostatic drug cladribine (2-CdA).
A technique of protein-DNA flow cytometry was applied to characterize cell cycling, and to assess the cytotoxicity of cladribine (2-chloro-2'deoxyadenosine) toward seven dissociated cultures of human primary brain tumors (anaplastic astrocytoma and glioblastoma multiforme) grown in vitro from surgical biopsies. Control cytograms were suggestive of that a clonogeneic fraction of the cell population consists mainly of cells with low protein content, which do not require increase in protein content before entering the S phase of the cell cycle. Following 24 or 48 hours exposure to cladribine, 1 nM approximately 1 microM, no cytotoxic effect was evident in 4 cultures, whereas in two cases dose-dependent progressive block of the phase of the cell cycle was noted. In one case a massive cytotoxic effect resulted in disintegration of culture exposed to 100 nM of the drug. However, the treatment with cladribine was ineffective in a patient bearing the tumor which was the source for the last culture, suggesting that cytotoxicity in vitro may not be predictive of clinical response.
Grieb
P
P
Department of Neurophysiology, Polish Academy of Sciences, Warszawa.
Skierski
J
J
Jagielski
J
J
Ryba
M
M
Mossakowski
M J
MJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001254:Astrocytoma / Q000473:pathology*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D017338:Cladribine / Q000008:administration & dosage / Q000494:pharmacology*; D046508:Culture Techniques; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D017338:Cladribine