In vitro cellular characteristics and survival responses of human astrocytoma clones to chloroethyl-nitrosoureas and dianhydrogalactitol

Three permanent clones were derived from a single astrocytoma cell line and were characterized for in vitro cell kinetics, chromosomal properties and for their responses to the anticancer drugs: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU); 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCC...

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Bibliographic Details
Published in:Investigational new drugs 1983-06, Vol.1 (2), p.129-137
Main Authors: Rubin, N H, Casartelli, C, Macik, B G, Boerwinkle, W R, Barranco, S C
Format: Article
Language:English
Subjects:
Astrocytoma - drug therapy
Astrocytoma - genetics
Astrocytoma - pathology
Brain Neoplasms - drug therapy
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Cell Line
Cell Survival - drug effects
Cells, Cultured
Clone Cells
Dianhydrogalactitol - pharmacology
DNA, Neoplasm - biosynthesis
Humans
Kinetics
Nitrosourea Compounds - pharmacology
Ploidies
Sugar Alcohols - pharmacology
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Summary:Three permanent clones were derived from a single astrocytoma cell line and were characterized for in vitro cell kinetics, chromosomal properties and for their responses to the anticancer drugs: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU); 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU); 1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidyl-1-nitrosourea) (PCNU); and 1,2:5,6-dianhydrogalactitol (GAL); all of which have been shown to cross the blood brain barrier. The clones showed different population doubling times, saturation densities, plating efficiencies, chromosome counts, ploidy, cell cycle phase distributions and DNA indices. The only positive correlation among these parameters was between the population doubling times and the modal chromosome numbers; the lower the chromosome number, the shorter the doubling time. No correlation was observable between any of the cellular properties and responses to the four drugs. The clones showed a differential sensitivity to the nitrosoureas, seen maximally as a 600-fold difference in survival between two of the clones treated with the same dose of BCNU. In contrast, the clones exhibited almost identical and uniform sensitivities to galactitol, suggesting that this agent exerted its cytotoxic effects by similar mechanisms in each of the clones. By comparison BCNU (at the tested doses and duration of drug exposure used in this study) was found to be the most effective of the agents tested.
ISSN:0167-6997
1573-0646
DOI:10.1007/BF00172071