C6 CELLS CROSS-RESISTANT TO CISPLATIN AND RADIATION

Malignant gliomas are relatively resistant to radiation and chemothera py. To investigate whether cisplatin (cis-diamminedichloroplatinum (II ), CDDP) causes resistance we pretreated C6 cells with 10(-6) M CDDP f or 24 hours and then tested their sensitivity in a colorimetric assay. Pretreated cells developed resistance to CDDP (resistance factor 2.0) and radiation (survival after 9 Gy Co-60: 36.4% +/- 5.5 versus 28.6% +/- 5.2, p=0.005). Glutathione levels of pretreated cells were higher (51.7 +/- 13.8 ng/mg protein) than in wt cells (40.4 +/- 13.2 p=0.029) . Addressing the mechanisms we established 4 wild type subclones with different CDDP sensitivities. However, cross-resistance to CDDP (survi val: 60.7% +/- 3.5 versus 7.2% +/- 0.5, respectively p=<0.001) and rad iation (29.7% +/- 2.6 versus 12.9% +/- 0.8, p=<0.001) could also be in duced in a subclone showing involvement of mutation. These data sugges t that CDDP cart induce resistance mediated via induced mutation and i ncreased GSH levels.