Abstract
DNA double-strand break (DSB) induction and repair have been widely studied in radiation therapy (RT); however little is known about the impact of very low exposures from repeated computed tomography (CT) scans for the efficiency of repair. In our current study, DSB repair and kinetics were investigated in side-by-side comparison of RT treatment (2 Gy) with repeated diagnostic CT scans (≤20 mGy) in human breast epithelial cell lines and lymphoblastoid cells harboring different mutations in known DNA damage repair proteins. Immunocytochemical analysis of well known DSB markers γH2AX and 53BP1, within 48 h after each treatment, revealed highly correlated numbers of foci and similar appearance/disappearance profiles. The levels of γH2AX and 53BP1 foci after CT scans were up to 30% of those occurring 0.5 h after 2 Gy irradiation. The DNA damage repair after diagnostic CT scans was monitored and quantitatively assessed by both γH2AX and 53BP1 foci in different cell types. Subsequent diagnostic CT scans in 6 and/or 12 weeks intervals resulted in elevated background levels of repair foci, more pronounced in cells that were prone to genomic instability due to mutations in known regulators of DNA damage response (DDR). The levels of persistent foci remained enhanced for up to 6 months. This “memory effect” may reflect a radiation-induced long-term response of cells after low-dose x-ray exposure.
Highlights
Computed tomography (CT) and radiotherapy (RT) are currently used for diagnosis and treatment of different diseases, and both rely on ionizing radiation (IR)
Decades [3], and recurrent radiological imaging procedure impacts higher cumulative radiation doses to patients than anticipated [4] thereby raising concerns about the possible risks associated with diagnostic ionizing radiation exposure, since evidence has indicated the presence of residual DNA double-strand breaks (DSBs) in human cells exposed to very low radiation doses [5, 6] and probably less efficient repair of DSBs induced by low doses [7]
The CT treatment evoked about 20–25% the level of gH2AX and 53BP1 foci compared with the 2 Gy treatment
Summary
Computed tomography (CT) and radiotherapy (RT) are currently used for diagnosis and treatment of different diseases, and both rely on ionizing radiation (IR). The cumulative risk of cancer from diagnostic CT scans has been estimated between 1.5 and 2.0% in the United States [10] and ranged from 0.6 to 1.8% in another 13 developed countries [11] with younger persons at the highest risk due to their possibly increased radiosensitivity and longer life expectancy [11,12,13]. These estimates are based on the linear non-threshold model, suggesting that cellular effects occur proportionally to ionizing radiation exposure at all levels; no point can be considered risk-free [14]. Others have suggested the presence of a damage threshold determining the efficiency of repair [5, 15], especially in terms of the hyper-radiosensitivity phenomenon, which describes radiation survival response of mammalian cells at doses below 0.5 Gy (or at very low doses below 10 cGy) after acute exposure [16]
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