Contrast Medium–enhanced Radiation Damage Caused by CT Examinations

Grudzenski, Saskia; Kuefner, Michael A.; Heckmann, Martina; Uder, Michael; Löbrich, Markus

doi:10.1148/radiol.2533090468

Cited by 86 publications

(118 citation statements)

References 28 publications

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“…It can be assumed that a cause of increased DSB as a response to contrast media can be an enhanced photoelectric absorption in the iodine atoms in the medium and consecutive exposure of adjacent lymphocytes [21]. Another study cast doubt on the effect of contrast agents due to in-vitro tests.…”

Section: Review 874mentioning

confidence: 99%

Radiation Induced DNA Double-Strand Breaks in Radiology

Kuefner

Brand

Engert

et al. 2015

Fortschr Röntgenstr

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Background !Shortly after the discovery of X-ray radiation, its detrimental effect on biological tissue was observed. The increasing number of X-raybased examinations in recent decades has reAbstract ! Shortly after the discovery of X-rays, their damaging effect on biological tissues was observed. The determination of radiation exposure in diagnostic and interventional radiology is usually based on physical measurements or mathematical algorithms with standardized dose simulations. γ-H2AX immunofluorescence microscopy is a reliable and sensitive method for the quantification of radiation induced DNA double-strand breaks (DSB) in blood lymphocytes. The detectable amount of these DNA damages correlates well with the dose received. However, the biological radiation damage depends not only on dose but also on other individual factors like radiation sensitivity and DNA repair capacity. Iodinated contrast agents can enhance the x-ray induced DNA damage level. After their induction DSB are quickly repaired. A protective effect of antioxidants has been postulated in experimental studies. This review explains the prinicple of the γ-H2AX technique and provides an overview on studies evaluating DSB in radiologic examinations. Key Points:▶ Radiologic examinations including CT and angiography induce DNA double-strand breaks. Even after mammography a slight but significant increase is detectable in peripheral blood lymphocytes.▶ The number of radiation induced doublestrand breaks correlates well with the radiation dose.▶ Individual factors including radiation sensitivity, DNA repair capacity and the application of iodinated contrast media has an influence on the DNA damage level. This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.sulted in the heightened importance of radiation dosage and protection as clinical topics [1, 2]. Determination of dose exposure in diagnostic and interventional radiology is carried out primarily using physical methods based on standardized phantoms or relying on mathematical dosage simulations. Such estimates can determine the exposure quite well, but supply no information regarding the interaction of radiation in the patient's body. Nowadays there are indications that biological radiation damage is not solely dependent on the applied dosage, but is also related to additional individual factors that cannot be sufficiently determined using established dosimetric methods. Earlier approaches to biological dosimetry were not sensitive enough for the dosage range used in radiology [3]. Double-stand breaks (DSB) are considered the most relevant radiation-induced damage to deoxyribonucleic acid (DNA) [4]. Although such breakage is quickly repaired, defective repairs can result in mutations, causing carcinogenesis [5, 6]. An immunofluorescence microscopic approach, which is much more sensitive than previous biological processes, allows the determination of individual DNA DSB in peripheral blood lymphocytes, thus allowing an accurate estimation of the biolog...

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Section: Review 874mentioning

confidence: 99%

Radiation Induced DNA Double-Strand Breaks in Radiology

Kuefner

Brand

Engert

et al. 2015

Fortschr Röntgenstr

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“…Because this technology detects single isolated DSBs in single cells, it has exceptional sensitivity and can monitor the effect of IR doses of a few mGy (20,21). Not surprisingly, γH2AX foci analysis has been applied to assess radiation doses encountered by humans during diagnostic medical procedures, such as computed tomography scanning (22)(23)(24)(25). Moreover, this technology can be applied to different tissues (26,27) and is becoming the gold standard for various biodosimetric applications (28,29).…”

Section: Significancementioning

confidence: 99%

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Mirsch

Tommasino

Frohns

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Charged particles are increasingly used in cancer radiotherapy and contribute significantly to the natural radiation risk. The difference in the biological effects of high-energy charged particles compared with X-rays or γ-rays is determined largely by the spatial distribution of their energy deposition events. Part of the energy is deposited in a densely ionizing manner in the inner part of the track, with the remainder spread out more sparsely over the outer track region. Our knowledge about the dose distribution is derived solely from modeling approaches and physical measurements in inorganic material. Here we exploited the exceptional sensitivity of γH2AX foci technology and quantified the spatial distribution of DNA lesions induced by charged particles in a mouse model tissue. We observed that charged particles damage tissue nonhomogenously, with single cells receiving high doses and many other cells exposed to isolated damage resulting from high-energy secondary electrons. Using calibration experiments, we transformed the 3D lesion distribution into a dose distribution and compared it with predictions from modeling approaches. We obtained a radial dose distribution with sub-micrometer resolution that decreased with increasing distance to the particle path following a 1/r 2 dependency. The analysis further revealed the existence of a background dose at larger distances from the particle path arising from overlapping dose deposition events from independent particles. Our study provides, to our knowledge, the first quantification of the spatial dose distribution of charged particles in biologically relevant material, and will serve as a benchmark for biophysical models that predict the biological effects of these particles.C harged particles, including protons, α-particles, and heavy ions, are increasingly used in cancer radiotherapy and represent a significant component of the natural background irradiation on earth and in space (1-3). Their biological effect is often very different from that of photons (X-or γ-rays), largely because charged particles deposit their energy along a track, whereas photons produce a fairly homogeneous dose distribution. Linear energy transfer (LET; typically given in units of keV/μm) has been introduced as a parameter to describe the amount of energy that charged particles deposit along their track. Particles with high LET are densely ionizing and typically biologically more effective than photons or low-LET particles. Energy deposition along a particle track is not restricted to the path itself (the so-called "track core"), but extends laterally into an area known as the penumbra of the particle, which can reach considerable distances for high-energy particles. Energy deposition in the penumbra arises from energetic secondary electrons, so-called δ-electrons, which are generated by ionization events of the charged particles and carry energy away from the immediate path into the penumbra. According to classical track structure theory, ∼50% of the total energy is deposited in the...

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“…Even higher doses are encountered during radiation therapy when tumor cells need to be inactivated. In contrast to these situations, radiodiagnostic investigations encompass much lower doses, with angiographic procedures and computer tomography scans representing high-dose radiodiagnostic examples in the dose range of several 10s of milligray (3)(4)(5)(6)(7). The most frequent radiodiagnostic examinations, x-ray scans, typically involve doses of less than 1 mGy.…”

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confidence: 99%

“…We and others have shown that foci arise in a 1:1 relationship to DSBs and that the kinetics of foci loss reflect repair of DSBs (16,(20)(21)(22). This technology has the sensitivity that is necessary to investigate milligray doses and can be applied to various cell types and tissue samples (4,5,(23)(24)(25)(26)(27).…”

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confidence: 99%

Inducible response required for repair of low-dose radiation damage in human fibroblasts

Grudzenski

Raths

Conrad

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Ionizing radiation (IR) induces a variety of DNA lesions among which DNA double-strand breaks (DSBs) are the biologically most significant. It is currently unclear if DSB repair is equally efficient after low and high doses. Here, we use γ-H2AX, phospho-ATM (pATM), and 53BP1 foci analysis to monitor DSB repair. We show, consistent with a previous study, that the kinetics of γ-H2AX and pATM foci loss in confluent primary human fibroblasts are substantially compromised after doses of 10 mGy and lower. Following 2.5 mGy, cells fail to show any foci loss. Strikingly, cells pretreated with 10 μM H 2 O 2 efficiently remove all γ-H2AX foci induced by 10 mGy. At the concentration used, H 2 O 2 produces single-strand breaks and base damages via the generation of oxygen radicals but no DSBs. Moreover, 10 μM H 2 O 2 up-regulates a set of genes that is also up-regulated after high (200 mGy) but not after low (10 mGy) radiation doses. This suggests that low radical levels induce a response that is required for the repair of radiation-induced DSBs when the radiation damage is too low to cause the induction itself. To address the in vivo significance of this finding, we established γ-H2AX and 53BP1 foci analysis in various mouse tissues. Although mice irradiated with 100 mGy or 1 Gy show efficient γ-H2AX and 53BP1 foci removal during 24 h post-IR, barely any foci loss was observed after 10 mGy. Our data suggest that the cellular response to DSBs is substantially different for low vs. high radiation doses.

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Contrast Medium–enhanced Radiation Damage Caused by CT Examinations

Abstract: The highly sensitive gammaH2AX foci assay shows that CM-enhanced radiation damage incurred in peripheral lymphocytes during CT. However, it is unknown whether long-term bioeffects of low-dose ionizing radiation from CT examinations, such as cancer, are increased by using CM.

Cited by 86 publications

References 28 publications

Radiation Induced DNA Double-Strand Breaks in Radiology

Radiation Induced DNA Double-Strand Breaks in Radiology

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Inducible response required for repair of low-dose radiation damage in human fibroblasts

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