Dalke C.,Institute of Radiation Biology |
Dalke C.,Helmholtz Center for Environmental Research |
Holzlwimmer G.,Institute of Pathology |
Calzada-Wack J.,Institute of Pathology |
And 3 more authors.
Journal of Radiation Research | Year: 2012
Genetic factors can modify susceptibility to the carcinogenic effect of ionising radiation. To establish if radioiodine-induced thyroid cancer is similarly genetically influenced, we studied F1 hybrid crosses between inbred mouse strains. Mice were perinatally exposed to iodine-131 and thyroid tissues examined after 18 months. Differences in the incidence and distribution of histological subtypes were quantified in relation to genetic background. As expected, the occurrence of thyroid lesions was significantly higher in irradiated mouse hybrids than in unirradiated controls. The most frequent alterations were the simple and the complex hyperplasias, followed by follicular adenoma and, less frequently, follicular carcinoma. Both the incidence and distribution of the histiotype were different between the hybrid mouse crosses. Crosses using JF1 mice (M. m. molossinus) produced F1 offspring that were more resistant to radiation-induced thyroid lesions. Sequence analysis of Braf, Ret, Hras, Krcis, Kit and Trp53, all genes that are commonly mutated in human thyroid cancers, did not show any evidence of mutation in the tumours. However, mic-rosatellite analysis of genomic DNA revealed frequent allelic imbalances in complex hyperplasia and follicular adenoma. We conclude that genetic background, in particular the JF1 genotype, confer differences in susceptibility to the carcinogenic effects of radioiodine on the thyroid.
News Article | October 27, 2016
More humans than ever are exposed to higher levels of ionizing radiation from medical equipment, airplanes, etc. A new study suggests that this kind of radiation may be a confounding factor in the neurodegenerative disease Alzheimer´s. Alzheimer's disease is the leading cause for dementia in the elderly, and its global prevalence is supposed to increase dramatically in the following decade - up to 80 million patients by 2040. - It is crucial that we investigate the potential factors behind this disease, says postdoc Stefan J. Kempf, University of Southern Denmark. His research focuses on possible connections between radiation and cognitive impairments. In a new study, he and an international consortia involving colleagues from Italy, Japan, Germany and Denmark show that low doses of ionising radiation induce molecular changes in the brain that resemble the pathologies of Alzheimer's. The study has been published in Oncotarget. Co-authors are from Institute of Radiation Biology/Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health and Institute for Environmental Sciences in Japan. Large numbers of people of all age groups are increasingly exposed to ionizing radiation from various sources. Many receive chronic occupational exposure from nuclear technologies or airline travel. The use of medical diagnostics and therapeutic radiology has increased rapidly - for example more than 62 million CT scans per year are currently carried out in USA. Approximately one third of all diagnostic CT examinations are scans of the head region. - All these kinds of exposures are low dose and as long as we talk about one or a few exposures in a lifetime I do not see cause for concern. What concerns me is that modern people may be exposed several times in their lifetime and that we don't know enough about the consequences of accumulated doses, says Stefan J. Kempf. Recent data suggest that even relatively low radiation doses, similar to those received from a few CT scans, could trigger molecular changes associated with cognitive dysfunction. In their new study, the researchers have elucidated molecular alterations in the hippocampus of mice. The hippocampus is an important brain region responsible for learning and memory formation and it is known to be negatively affected in Alzheimer´s. The authors induced changes in the hippocampus by two kinds of chronic low-dose-rate ionizing radiation treatments. The mice were exposed to cumulative doses of 0.3 Gy or 6.0 Gy given at low dose rates of 1 mGy over 24 hours or 20 mGy over 24 hours for 300 days. - Both dose rates are capable of inducing molecular features that are reminiscent of those found in the Alzheimer's disease neuropathology, says Stefan J. Kempf. When a patient gets a head scan, the doses varies between 20 and 100 mGy and lasts for around one minute. When a person flies, he or she gets exposure to ionising radiation coming from space but the rates are by far smaller than a CT scan. - When you compare these figures you will find that we exposed the mice to a more than 1000 times smaller cumulative dose than what a patient gets from a single CT scan in the same time interval. And even then we could see changes in the synapses within the hippocampus that resemble Alzheimer´s pathology. According to Stefan J. Kempf, the data indicate that chronic low-dose-rate radiation targets the integration of newborn neurons in existing synaptic wires. Paper: Chronic low-dose-rate ionising radiation affects the hippocampal phosphoproteome in the ApoE?/? Alzheimer mouse model. Forfattere: Stefan Kempf, Dirk Janik, Zarko Barjaktarovic, Ignacia Braga-Tanaka III, Satoshi Tanaka, Frauke Neff, Anna Saran, Martin Røssel Larsen, Soile Tapio. OncoTarget, 20. september 2016. Postdoc Stefan J. Kempf, Department of Biochemistry and Molecular Biology University of Southern Denmark. email@example.com Phone: +45 65508929
Moertl S.,Institute of Radiation Biology |
Ahne F.,Institute of Radiation Biology
Methods in Molecular Biology | Year: 2012
Base excision repair (BER) is an important mechanism to maintain genomic stability. Here we offer a set of protocols to quantitatively analyze BER capacity in whole cell-free yeast extracts. Cell-free yeast extracts were obtained by a French press procedure and repair capacities were measured by using oligonucleotide substrates. Repair products were separated by polyacrylamide gel electrophoresis and detected by autoradiography. These set of methods allow the analysis of different kinds of base damage and of individual mechanistic steps within BER. We used these protocols to investigate a new role of the DNA double strand break repair protein XRS1 in BER (1). © 2012 Springer Science+Business Media New York.
PubMed | Institute of Radiation Biology
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2012
Base excision repair (BER) is an important mechanism to maintain genomic stability. Here we offer a set of protocols to quantitatively analyze BER capacity in whole cell-free yeast extracts. Cell-free yeast extracts were obtained by a French press procedure and repair capacities were measured by using oligonucleotide substrates. Repair products were separated by polyacrylamide gel electrophoresis and detected by autoradiography. These set of methods allow the analysis of different kinds of base damage and of individual mechanistic steps within BER. We used these protocols to investigate a new role of the DNA double strand break repair protein XRS1 in BER (1).
PubMed | Institute of Radiation Biology
Type: Journal Article | Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology | Year: 2013
Radiotherapy of thoracic and chest-wall tumours increases the long-term risk of radiation-induced heart disease. The aim of this study was to investigate the long-term effect of local heart irradiation on cardiac mitochondria.C57BL/6 and atherosclerosis-prone ApoE(-/-) mice received local heart irradiation with a single X-ray dose of 2 Gy. To investigate the low-dose effect, C57BL/6 mice also received a single heart dose of 0.2 Gy. Functional and proteomic alterations of cardiac mitochondria were evaluated after 40 weeks, compared to age-matched controls.The respiratory capacity of irradiated C57BL/6 cardiac mitochondria was significantly reduced at 40 weeks. In parallel, protein carbonylation was increased, suggesting enhanced oxidative stress. Considerable alterations were found in the levels of proteins of mitochondria-associated cytoskeleton, respiratory chain, ion transport and lipid metabolism. Radiation induced similar but less pronounced effects in the mitochondrial proteome of ApoE(-/-) mice. In ApoE(-/-), no significant change was observed in mitochondrial respiration or protein carbonylation. The dose of 0.2 Gy had no significant effects on cardiac mitochondria.This study suggests that ionising radiation causes non-transient alterations in cardiac mitochondria, resulting in oxidative stress that may ultimately lead to malfunctioning of the heart muscle.