Individual radiation sensitivity

Radiation Oncology

Head of Department:
Prof. Dr. med. Rainer Fietkau

Research group Radiation Sensitivity

Why are there people with different radiation sensitivity?

Individual radiation sensitivity describes how the cells of an individual can deal with the damage to DNA caused by radiation. This includes not only that the damage to the DNA is repaired, but also that information about the number and severity of the damage is adequately passed on within the cell. Furthermore, the cell must then react correctly and, for example, stop cell division or, in the case of particularly serious damage, ensure that it can never divide again. All these steps together are called damage processing.

Several hundred different proteins or genes are needed for damage processing. Even small changes (polymorphisms and mutations) in these genes can lead to an altered damage processing. This then means that humans are more sensitive to radiation and other agents that damage DNA.

Individual radiation sensitivity

Differences in the radiation sensitivity of 202 different individuals

As a result of the characteristics of these different genes, each person has a specific radiation sensitivity, which describes how the person can deal with the damage caused by radiation. Radiation sensitivity can be tested by various methods, e.g. by irradiating blood cells ex vivo and then examining the repair and further processing of the damage. We use as standard the examination of blood lymphocytes, which we irradiate with 2 Gy and then let grow. After 48 hours we examine in the first division phase which damages remained from the irradiation. This damage is expressed in breaks per division (breaks per metaphase) and above this, an increased radiation sensitivity can be very well reflected. If the values are increased to more than 0.55 fractions per metaphase, we strongly recommend reducing the daily doses of radiation therapy accordingly.

Genetic syndromes

There are a number of genetic diseases with different symptoms, which in addition often cause increased sensitivity to radiation. Better known syndromes are Fanconi Syndrome, Ataxia Telangiectatica and Nijmegen Breakage Syndrome. In all syndromes the degree of radiation sensitivity is not always the same. In Fanconi syndrome there are patients who are not increased and others who are significantly increased radiation sensitive.

Weitere genetische Syndrome mit erhöhter Strahlenempfindlichkeit sind:
Genetic syndromes with increased radiation sensitivity:
Ataxia Telangiectatica (ATM) ATLD / Mre11
Cockayne-syndrome Bloom-syndrome
DNA-PK Fanconi Anämie   
Ligase IV Nijmegen Breakage syndrome
Rett syndrome Rothmund-Thomson-syndrome
SCID-Artemis Trichothiodsytrophie
Werner-syndrome Xeroderma pigmentosum

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Familial cancer diseases

However, there are also genes that are passed on in families that do not cause disease, but which lead to familial cancer and may also be associated with increased radiation sensitivity. The cause of familial cancer may be increased sensitivity to radiation, which may also cause increased sensitivity to other agents such as carcinogenic chemicals. The impaired damage processing then leads to increased changes in the genes and can cause cancer. An indication of such a constellation are several cases of cancer in siblings, parents and grandparents. A young age of illness earlier than before the age of 45 to 50 and the occurrence of several cancers also indicate a possible increased individual radiation sensitivity.

 
Familial cancers are present in the following syndromes:
Familial breast cancers (BRCA1/2)
Li Fraumeni syndrome
HNPCC / Lynch syndrome

Publications on the subject:

Veröffentlichungen
Rate of individuals with clearly increased radiosensitivity rise with age both inhealthy individuals and in cancer patients. (2018) Barbara Schuster, Anna Ellmann, Theresa Mayo, Judith Auer, Matthias Haas, Markus Hecht, Rainer Fietkau, Luitpold V. Distel; BMC Geriatrics 18:105
Fahrig A, Koch T, Lenhart M, Rieckmann P, Fietkau R, Distel L, Schuster B. (2018) Lethal outcome after pelvic salvage radiotherapy in a patient with prostate cancer due to increased radiosensitivity : Case report and literature review. Strahlenther Onkol.
Ex Vivo Apoptosis in CD8+ Lymphocytes Predicts Rectal Cancer Patient Outcome. (2016) Sebastian Winkler, Philipp Hoppe, Marlen Haderlein, Markus Hecht, Rainer Fietkau, and Luitpold V. Distel
Distinct increased outliers among 136 rectal cancer patients assessed by γH2AX; Jana Kroeber, Barbara Wenger, Manuela Schwegler, Christoph Daniel, Manfred Schmidt, Cholpon S Djuzenova, Bülent Polat, Michael Flentje, Rainer Fietkau and Luitpold V Distel (2015) Radiation Oncology
PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals; Barbara Wenger, Manuela Schwegler, Maria Brunner, Christoph Daniel, Manfred Schmidt, Rainer Fietkau and Luitpold V Distel (2014) BMC Geriatr 14: 42.
Individual radiosensitivity in a breast cancer collective is changed with the patients’ age (2013) Judith Auer, Ulrike Keller, Manfred Schmidt, Oliver Ott, Rainer Fietkau, Luitpold V. Distel
Prädiktion von Normal- und Tumorreaktion nach Strahlentherapie (2012) E. Dikomey  J. Dahm-Daphi L. Distel
Chromosomal Instability in Ataxia Telangiectasia (2008) Luitpold V. Distel and Susann Neubauer
Individual differences in chromosomal aberrations after in vitro irradiation of cells from healthy individuals, cancer and cancer susceptibility syndrome patients (2006) Luitpold V. Distela, Susann Neubauer, Ulrike Keller, Carl N. Sprung, Rolf Sauer, Gerhard G. Grabenbauer
Breakpoint locations within chromosomes 1, 2, and 4 of patients with increased radiosensitivity (2006) Silke Schilling, Ulrike Keller, Carl N. Sprung, Anja Weise, Gerhard G. Grabenbauer, Rolf Sauer, Luitpold Distel
Cytogenetic instability in young patients with multiple primary cancers (2005) Ulrike Keller, Gerhard Grabenbauer, Alma Kuechler, Carl N. Sprung, Elisabeth Müller, Rolf Sauer, Luitpold Distel
Inter-relation of apoptosis and DNA double-strand breaks in patients with multiple primary cancers (2005) Britta C. Kaminski, Gerhard G. Grabenbauer, Carl N. Sprung, Rolf Sauer
and Luitpold V.R. Distel
Impact of Various Parameters in Detecting Chromosomal Aberrations by FISH to Describe Radiosensitivity (2004) Ulrike Keller, Alma Kuechler, Thomas Liehr, Elisabeth Müller, Gerhard Grabenbauer, Rolf Sauer, Luitpold Distel
Radiation sensitivity testing by fluorescence in-situ hybridization: how many metaphases have to be analysed? (2004) U. KELLER, G. GRABENBAUER, A. KUECHLER, R. SAUER and L. DISTEL
Fatal Toxicity Following Radio- and Chemotherapy of Medulloblastoma in a Child With Unrecognized Nijmegen Breakage Syndrome (2003) Luitpold Distel, Susann Neubauer, Raymonda Varon, Wolfgang Holter, and Gerhard Grabenbauer

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Working Group Individual Radiation Sensitivity

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