In vivo formation and repair of DNA double-strand breaks after computed tomography examinations

Abstract

Ionizing radiation can lead to a variety of deleterious effects in humans, most importantly to the induction of cancer. DNA doublestrand breaks (DSBs) are among the most significant genetic lesions introduced by ionizing radiation that can initiate carcinogenesis. We have enumerated ␥-H2AX foci as a measure for DSBs in lymphocytes from individuals undergoing computed tomography examination of the thorax and͞or the abdomen. The number of DSBs induced by computed tomography examination was found to depend linearly on the dose-length product, a radiodiagnostic unit that is proportional to both the local dose delivered and the length of the body exposed. Analysis of lymphocytes sampled up to 1 day postirradiation provided kinetics for the in vivo loss of ␥-H2AX foci that correlated with DSB repair. Interestingly, in contrast to results obtained in vitro, normal individuals repair DSBs to background levels. A patient who had previously shown severe side effects after radiotherapy displayed levels of ␥-H2AX foci at various sampling times postirradiation that were several times higher than those of normal individuals. ␥-H2AX and pulsed-field gel electrophoresis analysis of fibroblasts obtained from this patient confirmed a substantial DSB repair defect. Additionally, these fibroblasts showed significant in vitro radiosensitivity. These data show that the in vivo induction and repair of DSBs can be assessed in individuals exposed to low radiation doses, adding a further dimension to DSB repair studies and providing the opportunity to identify repair-compromised individuals after diagnostic irradiation procedures.␥-H2AX foci ͉ ionizing radiation ͉ low radiation doses ͉ radiosensitivity ͉ blood lymphocytes I onizing radiation (IR) exposure is frequently encountered in a person's life. Sources of natural radiation include cosmic rays that come from outer space and the sun and radioactive substances that exist in earth and inside the human body. In addition to occupational exposure, flights at high altitude, manned space exploration, and radiological terrorism represent significant sources of radiation risk for part of the population. Diagnostic x-ray procedures including screening tests for cancer are the largest man-made source of radiation exposure, accounting for Ϸ14% of the total exposure level worldwide (1-4).Exposure to IR can induce leukemia and other cancers. It is assumed that damage to DNA in the nucleus of a single cell can initiate carcinogenesis. Among the different types of lesions induced, DNA double-strand breaks (DSBs) are considered to be the most relevant of the deleterious effects of IR (5, 6). Remarkably, even a single radiation track and, hence, the smallest possible quantity of IR can produce this kind of damage. Estimates of cancer risk from exposure to IR are based on epidemiological studies of exposed human populations, especially the atomic bomb survivors of Hiroshima and Nagasaki. These studies have provided relatively reliable estimates of risk for moderate to high doses (1, 2). The lowest dose...

X-irradiation of cells on glass slides has a dose doubling impact

“…Recently, γH2AX foci analysis has become a widely used tool to quantify DSBs on a single cell level after IR (2). γH2AX foci numbers of 30-35 per Gy per G1 cell have been reported (3)(4)(5)(6)(7)(8) suggesting that there is a 1:1 correlation between γH2AX foci and DSBs after IR of nonreplicating cells. However, the precise DSB induction yields following irradiation can depend on a number of factors (see, eg, (9)) and, we show here, are critically dependent upon the surface upon which the cells are grown and irradiated.…”

Carotid CTA: Radiation Exposure and Image Quality with the Use of Attenuation-Based, Automated Kilovolt Selection

“…6 Biologic experiments have demonstrated that the number of DNA double-strand breaks is closely related to the applied dose. 3,7 Several techniques for CT dose reduction, maintaining image quality on a diagnostic level, became a hot topic in clinical research. [8][9][10][11] Automated attenuation-based tube current modulation or so-called automatic exposure control techniques are widely used.…”

Should human chondrocytes fly? The impact of electromagnetic irradiation on chondrocyte viability and implications for their use in tissue engineering

“…It is well known that some components of DNA are most sensitive to radiation and that repair mechanisms of the cell are often ineffective due to these irreversible damages [10,12]. Lö brich et al described radiation-induced damage to DNA and that aggregation of base damage can lead to cell death, mutations and even generation of cancer [10,12].…”

“…During irradiation the cell cultures of the experimental groups were always maintained at 4°C using ice cooling [12].…”