Dose rate-driven responses to ionizing radiation in CBA/Ca and C57BL/6N evaluated using benchmark dose (BMD) modeling

Area of Science:

• Environmental Health
• Radiation Biology
• Genotoxicology

Background:

• Dose rate significantly impacts biological effects of ionizing radiation.
• Understanding dose rate effects is crucial for accurate radiation risk assessment.

Purpose of the Study:

• Investigate genotoxic and phenotypic effects of varying gamma radiation dose rates.
• Maintain a constant total dose (3 Gy) across different exposure scenarios.
• Identify sensitive biomarkers for dose rate prediction.

Main Methods:

• Exposed mice (CBA/CaOla, C57BL/6N) to 60Co gamma radiation at low (2.5 mGy/h), medium (10 mGy/h), and high (100 mGy/h) dose rates.
• Assessed cellular stress via micronuclei in reticulocytes, DNA damage (comet assay), mitochondrial DNA alterations (ddPCR), and protein carbonylation.
• Performed benchmark dose (BMD) analysis on liver transcriptomic data.

Main Results:

• Micronucleus formation in reticulocytes showed a highly sensitive log-linear dose rate response (R²=0.98).
• Mitochondrial DNA copy number varied with strain and dose rate; no significant changes in common deletions or protein carbonylation.
• Chronic low dose rate exposure reduced testis weights by ~60%.

Conclusions:

• Micronucleus assay in reticulocytes is a sensitive biomarker for radiation dose rate prediction.
• BMD analysis of transcriptomic data revealed shared radiation responses.
• Integrating adverse effect analysis with BMDL estimations enhances dose rate-response characterization for improved risk assessment.