Programmed cell death in response to chemotherapeutic agents in human germ cell tumour lines.
Testicular germ cell tumours are amongst the most chemosensitive neoplasms both in vivo and in vitro. In the present study we demonstrate that following exposure to drugs used in chemotherapeutic treatment of testicular germ cell cancer tumour cells undergo death by apoptosis. Thus, after exposure of the GCT27 embryonal carcinoma cell line to cisplatin, we observed the degradation of DNA into oligonucleosomal fragments, which is a hallmark of apoptosis. Furthermore, light, fluorescence and electron microscopy reveal the presence of condensed abnormal shaped nuclear chromatin which is characteristic of apoptosis. Changes diagnostic of apoptosis were also observed following (a) cisplatin treatment of the GCT48 and Susa embryonal carcinoma cell lines and the GCT44 yolk sac tumour cell line and (b) etoposide treatment of the GCT27 and Susa cell lines. When the GCT27 cell line was treated with 15 microns cisplatin, apoptosis was first observed at 6-9 h and greater than 90% of cells were dead within 24 h. Apoptosis was not blocked when cisplatin-treated cells were incubated in the presence of cycloheximide, although this agent did cause a 4-6 h delay in the onset of cell death. In addition, we demonstrated that the GCT27 cell line can be induced to undergo apoptosis by exposure to low concentrations of the calcium ionophore, ionomycin. These observations show that germ cell tumours are remarkably sensitive to a range of agents that act by different mechanisms. They are triggered to undergo apoptosis rapidly by a mechanism that is not blocked by inhibitors of protein synthesis.
Huddart
R A
RA
Section of Molecular Carcinogenesis, Institute of Cancer Research, Sutton, Surrey, U.K.
Titley
J
J
Robertson
D
D
Williams
G T
GT
Horwich
A
A
Cooper
C S
CS
D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D018237:Germinoma / Q000473:pathology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D013736:Testicular Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015759:Ionomycin; D005047:Etoposide; D003513:Cycloheximide; D002945:Cisplatin