Appearance of 1-2 Mbp giant DNA fragments as an early common response leading to cell death induced by various substances that cause oxidative stress.
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| Abstract |
The effects of oxidative stress on double strand DNA breakage were examined in T-24 human bladder tumor cells using various active oxygen producing agents such as hydrogen peroxide (H2O2), bleomycin (BLM), neocarzinostatin (NCS), and x-ray irradiation. Analysis of the DNA by pulsed-field gel electrophoresis (PFGE) revealed that discrete giant DNA fragments of 1-2 Mbp and 200-800 kbp had accumulated in the nuclei of the treated cells. The 1-2 Mbp giant DNA fragments were first observed 2 h after the T-24 cells were exposed to the active oxygen producing agents, or irradiated with x-ray. The appearance and the amounts of 1-2 Mbp and 200-800 kbp giant DNA fragments seemed to depend on the concentration and the type of reagents used or the dose of x-ray. Following the accumulation of giant DNA fragments, another type of DNA fragmentation was detected and DNA fragments smaller than 100 kbp accumulated in the nuclei of the cells irradiated with x-ray or treated with NCS. In addition, DNA ladder formation, which is characteristic of apoptosis, was observed. The giant DNA fragments appeared to arise as a consequence of double-stranded DNA breakage, which occurred earlier than cell lysis, as assessed by 51Cr release. These findings indicate that the formation of giant DNA fragments is a specific characteristic of cells responding to oxidative stress, and it may be an initial event that leads to cell death.
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| Authors | Y Higuchi, S Matsukawa |
| Journal | Free radical biology & medicine (Free Radic Biol Med) Vol. 23 Issue 1 Pg. 90-9 ( 1997) ISSN: 0891-5849 [Print] United States |
| PMID | 9165301 (Publication Type: Journal Article) |
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