Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in Apc^Min/+ mice

Abstract

Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60Co‐γ‐rays at a LDR (2.2 mGy h−1) or acutely exposed to 2.6 Gy HDR X‐rays (1.3 Gy min−1). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig‐a gene mutation assay), and levels of DNA lesions (Comet assay, single‐strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3‐ and 10‐fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The ApcMin/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560–569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society

Radiation-Induced Chromosomal Aberrations and Immunotherapy: Micronuclei, Cytosolic DNA, and Interferon-Production Pathway

“…The relationship between relative biological effectiveness (RBE) and LET, based on the data available in the literature, is shown in Figure 4 and has the typical trend observed for other endpoints, such as CA ( 68 ), mutations ( 69 ), cells killing ( 70 ), or neoplastic transformation ( 71 ). Also consistent with the sparing effect observed at low dose rate for most cellular endpoints, MN yields are reduced for chronic compared to acute exposure ( 72 , 73 ). MN have been often measured in PBL from individuals exposed to radiation because of nuclear accidents or for cancer therapy.…”

Increase of secondary mutations may be a drug-resistance mechanism for lung adenocarcinoma after radiation therapy combined with tyrosine kinase inhibitor

“…Based on the current practice of cancer treatment, this study puts forward some issues for medical community to think about from the perspective of a basic research, which is of innovative significance [24,25]. At present, the treatment of lung cancer in patients with TKI-resistant lung cancer who treated with or without radiotherapy refers to the simple TKI treatment.…”

A framework for exposure characterization and gamma dosimetry at the NMBU FIGARO irradiation facility

“…It is important to be aware that different setups require different approaches. For thin specimens exposed in air (such as plants) it is necessary to consider buildup conditions (or the lack thereof); for larger organisms in air (like mice) we may want to calculate whole-body absorbed dose rates for different orientations and positions of the animals in their cages and estimate an average (Graupner et al 2017); and for setups with soil or water habitats, we need to account for the variation in absorbed dose rates with depth due to attenuation and scattering in the media (Hurem et al 2017). Geant4 simulations are useful in all these cases, but are limited by the ease and accuracy by which setups can be modelled.…”