Dose-rate effect on proliferation suppression in human cell lines continuously exposed to γ rays

Area of Science:

• Radiobiology
• Cellular and Molecular Biology
• Radiation Oncology

Background:

• Radiation dose rate is a critical determinant of biological effects and human health risks.
• Previous research proposed the modified exponential (MOE) model, predicting an exponential decline in radiation risk with decreasing dose rate.
• Understanding dose-rate effects is crucial for accurate radiation risk assessment.

Purpose of the Study:

• To investigate the dose-rate effect on cell proliferation during continuous gamma-ray exposure.
• To evaluate the validity of the modified exponential (MOE) model in different cellular contexts and exposure phases.
• To identify mechanisms underlying radiation dose-rate sensitivity in both early and later phases of exposure.

Main Methods:

• Continuous gamma-ray irradiation of various cell lines (tumor cells, fibroblasts, leukocytes) at constant dose rates.
• Monitoring cell proliferation suppression over time (up to 1000 hours).
• Comparison of dose-rate effects in DNA repair-proficient cells versus cells with impaired DNA-PK or ATM pathways.

Main Results:

• Cell proliferation was suppressed during the early phase of exposure (up to 1000 h), irrespective of increasing total dose.
• This early-phase suppression followed the MOE model in DNA repair-proficient cells but not in cells with impaired DNA-PK or ATM.
• A dose-rate effect was observed in the later phase, even in mutant cell lines, suggesting a mechanism independent of DNA-PK and ATM.

Conclusions:

• Radiation risk in the early phase of continuous exposure is primarily determined by the dose rate, consistent with the MOE model in proficient cells.
• A distinct, DNA-PK/ATM-independent mechanism influences the dose-rate effect in the later phase of radiation exposure.
• These findings necessitate a nuanced understanding of radiation biology, distinguishing between early and late effects for accurate risk assessment.