Characterization and chemosensitivity of two cell lines derived from human glioblastomas.
We have characterized two human glioblastoma cell lines, which were designated as YH cells and AM cells. The two cell lines maintained morphological appearance observed in the primary culture and immunohistochemically expressed glial fibrillary acidic protein (GFAP) and S-100 protein. Population doubling time for YH cells and AM cells indicated 30 hours and 25 hours, respectively, in an exponential phase of culture. Inoculation of AM cells into athymic nude mice formed large tumors at a high incidence. As with chemosensitivity to chloroethylnitrosourea, O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in in vitro cultured cells as well as tumor specimens obtained at surgery. YH cells showed a high MGMT activity of 1196 fmol/mg and drug resistance to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. YH tumor specimens indicated an MGMT activity of 301 fmol/mg, which reflected poor effectiveness of ACNU chemotherapy in the clinical evaluation. AM cells had an extremely low MGMT activity of 16 fmol/mg and were vulnerable to ACNU. Original tumor specimens of AM cells however expressed a high value of 628 fmol/mg. Considering that ACNU chemotherapy was not effective in the both patients, an MGMT activity of original tumors related with responsiveness to ACNU. Discrepancy in an MGMT activity between the in vitro cell lines and the respective tumor specimens comes from selection of ACNU-sensitive cells or alteration in biological characteristics during long term culture. These results suggest that cell lines derived human brain tumors are useful targets for understanding the chemosensitivity of human malignant gliomas and for establishing a pertinent chemosensitivity test.
Izumu
I
I
Neurosurgical Service, Akita University Hospital, Japan.
Mineura
K
K
Watanabe
K
K
Kowada
M
M
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000031:analogs & derivatives; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007621:Karyotyping; D008297:Male; D008780:Methyltransferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009368:Neoplasm Transplantation; D015376:Nimustine / Q000494:pharmacology; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009778:Occipital Lobe; D010296:Parietal Lobe; D009418:S100 Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D005904:Glial Fibrillary Acidic Protein; D009418:S100 Proteins; D015376:Nimustine; C017139:1-(2-chloroethyl)-1-nitrosourea; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005038:Ethylnitrosourea