Special Issue "Radiation-Related Cancer 25 Years After Chernobyl"

Guest Editor
Prof. Dr. Horst Zitzelsberger
Department of Radiation Cytogenetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany
Website: http://www.helmholtz-muenchen.de/zyto/staff/director/index.html
E-Mail: zitzelsberger@helmholtz-muenchen.de
Phone: +49 89 318 73421
Fax: +49 89 318 72873
Interests: cytogenetics; chromosome aberrations; cancer cytogenetics; molecular cytogenetics; radiation biology; thyroid cancer; radiation-induced carcinogenesis; positional cloning of chromosomal breakpoints

Dear Colleagues,

The 26^th of April, 2011, marks the 25^th anniversary of the Chernobyl accident in northern Ukraine, the largest nuclear plant accident in history. As a consequence, approximately five million people were exposed to the radioactive fallout in the Russian Federation, Ukraine and Belarus. This nuclear disaster along with the atomic bomb explosions in Japan 65 years ago, called to mind the carcinogenic potential of ionizing radiation and its long-term health effects that arise in exposed populations. One of the most surprising health effects of the Chernobyl accident was the appearance and magnitude of cases of thyroid cancer in children that lived in the heavily contaminated areas. In the decades following the accident many researchers have looked at the biological effects occuring in cells that were exposed to radiation in order to understand the molecular mechanisms associated with radiation-related cancer. Although evidence of radiation-induced DNA damage, such as the induction of chromosome aberrations exists, there are only few indications of radiation-specific molecular markers in these tumors. In order to gain a better understanding of the specific actions of ionizing radiation in tumor development, it also might be helpful to identify radiation-specific gene alterations in tumors developed after medical irradiation. To mark the 25^th anniversary of the Chernobyl accident, a special issue of the journal Genes will be issued in order to shed light on knowledge about molecular mechanisms in radiation-related cancer. Authors are encouraged to submit original research articles and reviews reporting findings from studies on cancers of radiation-exposed cohorts. Also welcome are papers on animal or cell culture studies modeling the radiocarcinogenic process. This special issue is intented to provide an overview on current knowledge in the research of radiaton-related cancer.

Prof. Dr. Horst Zitzelsberger
Guest Editor

Submission

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Type of Paper: Review
Title: Biological Complexities in Carcinogenesis and Cancer Treatment: Impact of New Biological Paradigms
Author: Hossein Mozdarani
Affiliation: Dept of Medical Genetic, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran; E-Mail: mozdarah@modares.ac.ir
Abstract: Various known cellular and molecular events are involved in carcinogenesis. The main key events are involvement of DNA repair genes, p53, cell cycle check point genes, chromosomal rearrangements, apoptosis, contact inhibition and specific genes for each type of cancer. Similarly the main treatment protocols used for cancer treatment is using the same physical or chemical agents capable of inducing key events involved in cancer induction. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention by other biological processes such as bystander effect, abscopal effect, intrinsic radio sensitivity and radio adaptation. Implications for carcinogenesis of radiation‐induced bystander effects are both mechanistic and practical. They include induction of second cancers, perturbations to tissue social control and induction of genomic instability and delayed or immediate mutations in areas not receiving a direct deposition of energy. Bystander effects have consequences for DNA damagemutation‐cancer initiation paradigms of radiation carcinogenesis that provide the mechanistic justification for low‐dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system, mainly cell‐mediated immunity. It results from loss of growth stimulatory and/or immunosuppressive factors from the tumor. Until recently, the abscopal effect referred to the distant effects seen after local radiation therapy. However, the term should now be used interchangeably with distant bystander effect. The abscopal effect is still extremely controversial with known data that both support and refute the concept. Some affected patients with various types of cancers show higher intrinsic radiosensitivity. Among these are breast cancer patients which show distinct radiosensitivity compared to normal individuals. This effect which is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not known yet that this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. The other major concern for carcinogenesis is the phenomenon of radio adaptation or radiation hormesis. This process which protect cells from higher doses of radiation or radiomimic chemicals, might lead to escape of cells from mitotic death or apoptosis and put cells with lower amount of damage in the process of cancer induction. On the other hand this phenomenon might intervene with the routine treatment protocols.

Type of Paper: Review
Title: Modeling the Risk of Secondary Malignancies after Radiotherapy
Author: Uwe Schneider
Affiliation: Vetsuisse Faculty, University of Zürich, Switzerland and Radiotherapy Hirslanden AG, Rain 34, Aarau, Switzerland; E-Mail: uwe.schneider@uzh.ch
Abstract: In developed countries more than half of all cancer patients receive radiotherapy at some stage in the management of their disease. However, a radiation induced secondary malignancy can be the price of success if the primary cancer is cured or at least controlled. With the application of new radiation treatment modalities such as intensity modulated radiotherapy, intensity modulated arc-therapy, proton and heavy ion radiotherapy increased cancer cure rates are expected. However, with the application of these treatment techniques also a larger number of secondary cancers is expected. Some workers believe that we will see an increase in second malignancies due to the substantial increase in beam-on time of IMRT techniques to deliver the same target dose and the different distribution of dose (“low dose to a large volume”) compared to conventional treatment techniques. In addition, during proton and heavy ion radiotherapy neutrons are created and could also have an impact on secondary cancer incidence. Therefore it could be of great importance to know the risk for the patient to develop a cancer which could have been caused by the radiation treatment. The long term risks from modern radiotherapy treatment techniques have not yet been determined and are unlikely to become apparent for many years, due to the long latency time for solid tumor induction. Therefore there is a need to develop models for risk assessment based on the current knowledge of radiation induced carcinogenesis. In this report the current knowledge of the shape of the dose-response curve for radiation induced cancer for doses larger than a few Gy is reviewed. In patients who receive radiotherapy, parts of the patient volume can receive high doses of up to approximately 100 Gy and it is therefore of great importance to know the dose-response curve of the risk for the patient to develop a cancer which could have been caused by the radiation treatment. These dose-response curves are then used to model second cancer induction for radiotherapy patients based on the three-dimensional dose distribution of the treatment of the primary disease. Current models used for such risk estimates are reviewed.

Type of Paper: Review
Title: Gene Expression Signature of Radiation-induced Thyroid Tumors after External or Internal Exposure
Authors: Catherine Ory, Nicolas Ugolin, Martin Schlumberger, Paul Hofman and Sylvie Chevillard
Affiliation: CEA, DSV, IRCM, LCE, BP6, Fontenay-aux-Roses F-92265, France; E-Mail: catherine.ory@cea.fr
Abstract: Both external exposure and internal contamination to ionizing radiation are strong risk factors for the development of thyroid tumors. The identification of sets of molecular markers deregulated in radiation-induced thyroid tumors is crucial for the etiology diagnosis since neither the histological features nor genetic alterations are specific of the etiology. Our laboratory developed a unique strategy of transcriptome analysis which was applied to identify highly discriminating signatures in a series of secondary thyroid tumors developed in the radiation field of patients treated by radiotherapy, and in a previously published dataset including sporadic and post-Chernobyl tumors. The relevance of extrapolation of conclusions from tumors occurring after exposure to external radiation, such as radiotherapy treatment, to post-Chernobyl PTCs that occurred after internal 131I contamination will be discussed in regards to our results and analysis presented in others studies.