Caffeine induces a second wave of apoptosis after low dose-rate gamma radiation of HL-60 cells
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Colony-Forming Units Assay MeSH
- Apoptosis drug effects radiation effects MeSH
- Cell Cycle drug effects radiation effects MeSH
- Radiation Dosage MeSH
- Adaptation, Physiological drug effects radiation effects MeSH
- HL-60 Cells MeSH
- Caffeine pharmacology MeSH
- Humans MeSH
- Radiation-Sensitizing Agents pharmacology MeSH
- Radiation Tolerance drug effects MeSH
- Cell Survival drug effects radiation effects MeSH
- Dose-Response Relationship, Radiation MeSH
- Dose-Response Relationship, Drug MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Caffeine MeSH
- Radiation-Sensitizing Agents MeSH
Most cell lines that lack functional p53 protein are arrested in the G(2) phase of the cell cycle due to DNA damage. It was previously found that the human promyelocyte leukemia cells HL-60 (TP53 negative) that had been exposed to ionizing radiation at doses up to 10 Gy were arrested in the G(2) phase for a period of 24 h. The radioresistance of HL-60 cells that were exposed to low dose-rate gamma irradiation of 3.9 mGy/min, which resulted in a pronounced accumulation of the cells in the G(2) phase during the exposure period, increased compared with the radioresistance of cells that were exposed to a high dose-rate gamma irradiation of 0.6 Gy/min. The D(0) value (i.e. the radiation dose leading to 37% cell survival) for low dose-rate radiation was 3.7 Gy and for high dose-rate radiation 2.2 Gy. In this study, prevention of G(2) phase arrest by caffeine (2 mM) and irradiation of cells with low dose-rate irradiation in all phases of the cell cycle proved to cause radiosensitization (D(0)=2.2 Gy). The irradiation in the presence of caffeine resulted in a second wave of apoptosis on days 5-7 post-irradiation. Caffeine-induced apoptosis occurring later than day 7 post-irradiation is postulated to be a result of unscheduled DNA replication and cell cycle progress.
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