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.