Cisplatin induces radioprotection in human T98G glioma cells.

Malignant gliomas are often treated with cisplatin (cis-diamminedichloroplatinum(II), CDDP) and radiation but results remain unsatisfactory. To investigate whether CDDP induces radioresistance in glioma, T98G human glioblastoma cells were pretreated 5 times with 10(-6)M CDDP for 24 hours and then the sensitivity of wild type (wt) and pretreated cells towards radiation (9Gy 60Co) and CDDP was tested in a colorimetric assay (MIT). The growth rates of wt and pretreated cells were 1.8 +/-0.2 and 3.1 +/- 0.2 respectively (p = 0.000155) 216 hours post radiation. Pretreated cells also developed resistance to CDDP (resistance factor 2.35). Glutathione (GSH) which potentially mediates resistance to both treatments was measured. Incubation for 6 hours with 10(-5) M CDDP increased GSH levels by a factor of 2.28 (p < 0.0001). However, neither basal nor increased levels differed between wt and pretreated cells. These data show that CDDP pretreatment can induce resistance against radiation and CDDP independently of GSH.