Heterogeneous chemosensitivities of subpopulations of human glioma cells in culture.

Six karyotypically distinct clonal cell lines isolated from each of two freshly resected human malignant gliomas were examined for heterogeneity of morphology, in vitro growth rate, and chemosensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea and cis-diamminedichloroplatinum (II). Each clone was identified karyotypically as having come from the parent tumor. The karyotypic deviations were primarily numerical; chromosome numbers ranged from hypodiploid to near-tetraploid. Three morphological types were recognized: astrocyte-like; squamous-like; and fibroblast-like. The growth rates differed among the clones; the doubling times ranged from 48 to 84 hr in those from one tumor and from 72 to 252 hr in the other. Chemosensitivity was measured by cytotoxicity and/or colony-forming assay. In both assays and in both tumors, heterogeneity of chemosensitivity response to both drugs was demonstrated among the different clones from the same tumor. Dose-response curves from some clones differed statistically (log-probit analysis) from those of others, and when the curves were parallel, their 50% effective doses often differed. For the cytotoxicity assay, the 50% effective doses of BCNU ranged from 43 to 94 microgram/ml and for cis-diamminedichloroplatinum (II), from 29 to 340 microgram/ml. For the colony-forming assay, the 50% effective doses of 1,3-bis(2-chloroethyl)-1-nitrosourea ranged from 4.5 to 7.0 microgram/ml and for cis-diamminedichloroplatinum (II), from 0.35 to 1.40 microgram/ml. No correlation was evident between the chromosome number, morphology, growth rates, or chemosensitivities of the clones. These results identified heterogeneity of chemosensitivity among cellular subpopulations in human malignant gliomas.