BCNU-SENSITIVITY IN PARENTAL CELLS AND CLONES FROM 4 FRESHLY RESECTEDNEAR-DIPLOID HUMAN GLIOMAS - AN ASTROCYTOMA, AN ANAPLASTIC ASTROCYTOMA AND 2 GLIOBLASTOMAS MULTIFORME

We compared the BCNU sensitivity of 4 freshly resected tumors (astrocy toma WM, and malignant gliomas MK, MB, and AM) and their clones to the ir karyology. The majority of primary cells in all 4 tumors had near-d iploid chromosome numbers (2n+/-) and all were resistant to concentrat ions of BCNU exceeding 10mug/ml. Following in vitro cultivation, the c ells from tumors WM and MB retained their 2n+/- modal chromosome numbe r with little change in the complexity of the karyotype. In contrast, tumors MK and AM demonstrated a more unstable genome. The modal chromo some number of MK shifted from 45 to 86 and that of tumor AM from 45 t o 90. Karyotyping demonstrated additional ploidy changes and new marke r chromosomes in both tumors. The colony forming assay (CFA) performed on the in vitro cultivated cells demonstrated little change in the se nsitivity to BCNU in tumors WM and MB, while tumors MK and AM exhibite d greater than a one log cell kill at 10.0mug/ml and 15.0mug/ml BCNU, respectively The modal chromosome number and BCNU sensitivity followed a similar pattern in the 30 clones that were isolated; 21 clones with near-diploid and pseudodiploid chromosome numbers were all resistant to BCNU doses at or greater than 10mug/ml. In contrast, 9 clones isola ted from the 3 malignant gliomas with 3n+/- and 4n+/- modal chromosome numbers were sensitive to this concentration of BCNU. The karyotypes of the hyperdiploid clones were more complex; they contained 5 or more ploidy changes and/or had marker chromosomes. These studies confirm t he association of diploidy and BCNU-resistance in freshly resected mal ignant gliomas.