Related Experiment Videos
Oncogenic transformation through the cell cycle and the LET dependent inverse dose rate effect
C R Geard1, R C Miller, D J Brenner
1Center for Radiological Research, Columbia University, New York 10032, USA.
Radiation Protection Dosimetry
|January 1, 1994
Summary
X-ray irradiation of synchronized mouse cells revealed that oncogenic transformation significantly increased 10-fold when cells were in the G2 phase. Cell survival varied, with peaks of resistance in late G1 and late S phases.
Area of Science:
- Cell biology
- Radiation oncology
- Molecular carcinogenesis
Background:
- Understanding the cell cycle's influence on radiation-induced oncogenic transformation is crucial for radiation protection and therapy.
- Previous hypotheses suggested a dependence of the inverse dose rate effect on linear energy transfer (LET).
Purpose of the Study:
- To investigate the impact of cell cycle progression on X-ray-induced oncogenic transformation in mouse C3H/10T-1/2 cells.
- To determine specific cell cycle phases most sensitive or resistant to oncogenic transformation following irradiation.
Main Methods:
- Synchronized mouse C3H/10T-1/2 cells were obtained using a mitotic dislodgement technique.
- Cells were irradiated with 3 Gy of X-rays at various time points (0-18 hours) after cell cycle progression initiation.
- Oncogenic transformation frequency and cell survival fractions were analyzed at different cell cycle stages.
Main Results:
- A 10-fold enhancement in oncogenic transformation was observed for cells irradiated during a specific 2-hour window in the G2 phase, distinct from mitosis.
- Cell survival exhibited a 2.5-fold variation, with notable resistance peaks in the late G1 and late S phases.
- Irradiation in G1 and S phases resulted in lower transformation enhancement compared to the G2 phase.
Conclusions:
- The cell cycle, particularly the G2 phase, plays a critical role in modulating the outcome of radiation-induced oncogenic transformation.
- These findings provide experimental evidence supporting theoretical models explaining the inverse dose rate effect in oncogenic transformation, linking it to cell cycle-dependent radiosensitivity.