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Radiation-induced apoptosis in different pH environments in vitro
1Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis 55455, USA.
Summary
Environmental acidity reversibly suppresses radiation-induced apoptosis in tumor cells. Lowering pH from 7.5 to 6.6 significantly reduced DNA fragmentation and prolonged G2 arrest after gamma irradiation.
Area of Science:
- Radiation oncology
- Cell biology
- Cancer research
Background:
- Apoptosis, or programmed cell death, is a critical mechanism for eliminating cancer cells.
- Tumor microenvironments can exhibit acidic pH due to metabolic activity, potentially influencing treatment efficacy.
- Understanding how environmental factors modulate radiation response is crucial for improving cancer therapy.
Purpose of the Study:
- To investigate the impact of environmental pH on radiation-induced apoptosis in tumor cells in vitro.
- To determine if acidic conditions affect DNA damage response and cell cycle progression following irradiation.
Main Methods:
- Mammary adenocarcinoma cells (SCK cells) were exposed to gamma radiation (2-12 Gy).
- Cells were incubated in media with varying pH levels (7.5 down to 6.4).
- Apoptosis was assessed using agarose gel electrophoresis, TUNEL staining, flow cytometry, and 3H-thymidine release assays. Cell cycle progression and clonogenicity were also analyzed.
Main Results:
- Gamma irradiation induced apoptosis in SCK cells at pH 7.5.
- Radiation-induced apoptosis and DNA fragmentation progressively decreased as pH was lowered.
- Acidic pH (6.6) reversibly suppressed DNA fragmentation and prolonged radiation-induced G2 cell cycle arrest.
Conclusions:
- An acidic tumor microenvironment reversibly suppresses radiation-induced apoptosis in SCK cells.
- Early apoptotic pathway steps, likely DNA breaks or upstream events, are inhibited by acidity.
- Prolonged G2 arrest in acidic conditions is linked to the suppression of apoptosis, suggesting a related mechanism.