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Genetically-Defined DNA Repair Capacity Determines the Extent of DNA Damage Accumulation in Healthy Mouse Tissues after Very Low Doses of Ionizing Radiation

Stefanie Schanz, Elias Flockerzi, Karola Schuberth and Claudia E. Rübe

The biological impact of low doses of ionizing radiation on human health and the genetic factors influencing whole organism radio-sensitivity at low doses are unclear. Using mouse strains that varied in genetic DNA repair capacity (C57BL/6, ATM +/+, ATM +/-, ATM -/-, SCID), we analyzed DNA damage in differentiated cell populations of healthy tissues after repeated low doses of radiation. After 2, 4, 6, 8, and 10 weeks of daily, low-dose radiation (10 mGy), persistent DNA damage foci were counted in the lung (bronchiolar and alveolar cells), heart (cardiomyocytes), and brain (cortical neurons). In all analyzed tissues, the gradual accumulation of DNA damage with increasing doses of fractionated radiation was observed. No verifiable threshold-dose was detected, even in repair-proficient organisms (C57BL/6, ATM +/+). The number of radiation-induced foci varied significantly between the different cell populations, suggesting differing vulnerability to ionizing radiation. Genetic DNA repair capacity also determined the cumulative amount of low-dose radiation damage, with the highest foci levels observed in repair-deficient ATM -/- and SCID mice. The repair capacity of ATM heterozygous mice (ATM +/-), however, was sufficient to cope with the DNA damage burden induced by repetitive low-dose radiation. Collectively, our findings suggest that even very low doses of DNA-damaging radiation increase the health risks of individuals, particularly of those with compromised DNA repair capacity.