C6 cells cross-resistant to cisplatin and radiation.

Malignant gliomas are relatively resistant to radiation and chemotherapy. To investigate whether cisplatin (cis-diamminedichloroplatinum(II), CDDP) causes resistance we pretreated C6 cells with 10(-6) M CDDP for 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 60Co: 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 (survival: 60.7% +/- 3.5 versus 7.2% +/- 0.5, respectively p = < 0.001) and radiation (29.7% +/- 2.6 versus 12.9% +/- 0.8, p = < 0.001) could also be induced in a subclone showing involvement of mutation. These data suggest that CDDP can induce resistance mediated via induced mutation and increased GSH levels.