Malignant gliomas are often treated with cisplatin (cis-diamminedichlo
roplatinum(II), CDDP) and radiation but results remain unsatisfactory.
To investigate whether CDDP induces radioresistance in glioma, T98G h
uman glioblastoma cells were pretreated 5 times with 10(-6) M CDDP for
24 hours and then the sensitivity of wild type (wt) and pretreated ce
lls towards radiation (9Gy Co-60) and CDDP was tested in a colorimetri
c assay (MTT). 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 radiati
on. Pretreated cells also developed resistance to CDDP (resistance fac
tor 2.35). Glutathione (GSH) which potentially mediates resistance to
both treatments was measured. Incubation for 6 hours with 10(-5) M CDD
P increased GSH levels by a factor of 2.28 (p<0.0001). However, neithe
r 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.