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.
Poppenborg
H
H
University Hospital of Münster, Department of Pediatric Hematology and Oncology, Germany.
Münstermann
G
G
Knüpfer
M M
MM
Hotfilder
M
M
Wolff
J E
JE
D000818:Animals; D001254:Astrocytoma; D001932:Brain Neoplasms; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000633:toxicity*; D002999:Clone Cells; D003037:Cobalt Radioisotopes; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005720:Gamma Rays; D005978:Glutathione / Q000378:metabolism; D009154:Mutation; D011836:Radiation Tolerance; D051381:Rats; D014407:Tumor Cells, Cultured
D003037:Cobalt Radioisotopes; D005978:Glutathione; D002945:Cisplatin