Cisplatin induces apoptosis in a human ovarian carcinoma cell line without concomitant internucleosomal degradation of DNA.
After treatment of the human ovarian carcinoma cell line, CH1, with cisplatin, cells detached from the culture dish in a time- and dose-dependent fashion. These cells showed morphological changes indicative of apoptosis. Their DNA had not been degraded into oligonucleosomal fragments, but the DNA had been cut into larger fragments (30 kbp) of a size associated with chromatin loops. We conclude that cisplatin killed these ovarian cells by inducing apoptosis. However, in these cells, apoptosis was not accompanied by internucleosomal degradation of DNA. Our data are consistent with the hypothesis that the introduction of a double-strand break at a specific site in the chromatin loops is an early event in apoptosis. This degradation is accompanied by morphologically observable changes in chromatin structure. Internucleosomal degradation, when it occurs, is a late event.
Ormerod
M G
MG
Section of Drug Development, Institute of Cancer Research: Royal Cancer Hospital, Sutton, United Kingdom.
O'Neill
C F
CF
Robertson
D
D
Harrap
K R
KR
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008854:Microscopy, Electron; D008970:Molecular Weight; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D009707:Nucleosomes; D002945:Cisplatin