Gene expression for biodosimetry and effect prediction purposes: promises, pitfalls and future directions – key session ConRad 2021

Abstract

Purpose

In a nuclear or radiological event, an early diagnostic or prognostic tool is needed to distinguish unexposed from low- and highly exposed individuals with the latter requiring early and intensive medical care. Radiation-induced gene expression (GE) changes observed within hours and days after irradiation have shown potential to serve as biomarkers for either dose reconstruction (retrospective dosimetry) or the prediction of consecutively occurring acute or chronic health effects. The advantage of GE markers lies in their capability for early (1–3 days after irradiation), high-throughput, and point-of-care (POC) diagnosis required for the prediction of the acute radiation syndrome (ARS).

Conclusions

As a key session of the ConRad conference in 2021, experts from different institutions were invited to provide state-of-the-art information on a range of topics including: (1) Biodosimetry: What are the current efforts to enhance the applicability of this method to perform retrospective biodosimetry? (2) Effect prediction: Can we apply radiation-induced GE changes for prediction of acute health effects as an approach, complementary to and integrating retrospective dose estimation? (3) High-throughput and point-of-care diagnostics: What are the current developments to make the GE approach applicable as a high-throughput as well as a POC diagnostic platform? (4) Low level radiation: What is the lowest dose range where GE can be used for biodosimetry purposes? (5) Methodological considerations: Different aspects of radiation-induced GE related to more detailed analysis of exons, transcripts and next-generation sequencing (NGS) were reported.

Keywords:

• Gene expression
• biodosimetry
• effect prediction
• radiation exposure
• high dose
• low dose

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the German Ministry of Defense. SAA and SAG were supported through the Center for High-Throughput Minimally-Invasive Radiation Biodosimetry, National Institute of Allergy and Infectious Diseases Grant Number U19 AI067773. AE was supported by the National Cancer Institute Grant Number R01 CA172067. Work was also performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

Notes on contributors

Patrick Ostheim

Patrick Ostheim, MD, is a Post-Doctoral Researcher of Radiobiology and a resident in Radiology at the Bundeswehr Institute of Radiobiology, Munich, Germany.

Sally A. Amundson

Sally A. Amundson, ScD, is an Associate Professor of Radiation Oncology and a faculty member of the Center for Radiological Research, Columbia University Irving Medical Center (CUIMC), New York, USA.

Christophe Badie

Christophe Badie, PhD, is a Researcher and leader of the Cancer Genetics and Cytogenetics group in the research department of Biological Effects at Public Health England’s Centre for Radiation, Chemical and Environmental Hazards (PHE CRCE), Faculty of Medicine at Imperial College of Science, Technology and Medicine, London, UK.

Dimitry Bazyka

Dimitry Bazyka, MD, is a Professor of radiobiology and Director-General of the National Research Centre for Radiation Medicine of the Academy of Medical Sciences of Ukraine (RCRM), Kyiv, Ukraine.

Angela C. Evans

Angela C. Evans is a Doctoral Student in the laboratory of Matthew A. Coleman at the University of California Davis, Sacramento, CA, USA and the Lawrence Livermore National Laboratory, Livermore, CA, USA.

Shanaz A. Ghandhi

Shanaz A. Ghandhi, PhD, is an Assistant Professor of Radiation Oncology at the Center for Radiological Research, Columbia University Irving Medical Center (CUIMC), New York, USA.

Maria Gomolka

Maria Gomolka, PhD, is a biologist and senior scientist in the working group biological radiation effects, biological dosimetry, Federal Office for Radiation Protection, Oberschleissheim, Germany.

Milagrosa López Riego

Milagrosa López Riego is a PhD Student at the Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden.

Peter K. Rogan

Peter K. Rogan, PhD, is a Professor in Biochemistry at the University of Western Ontario, London, Ontario, Canada, and cofounder of CytoGnomix Inc, London, Ontario, Canada.

Robert Terbrueggen

Robert Terbrueggen, PhD, is a Researcher and the Founder/CEO of DxTerity Diagnostics, Los Angeles, CA, USA.

Gayle E. Woloschak

Gayle E. Woloschak, PhD, is a Professor of Radiation Oncology and Radiology at the Feinberg School of Medicine, Radiation Oncology, Northwestern University, Chicago, IL, USA.

Frederic Zenhausern

Frederic Zenhausern, PhD, MBA, is a Professor of Radiation Oncology at the Department of Basic Medical Sciences, College of Medicine, The University of Arizona, Phoenix, AZ, USA, and Director of the Center for Applied Nanobioscience and Medicine, University of Arizona, Phoenix, AZ, USA.

Hanns L. Kaatsch

Hanns L. Kaatsch, MD, is a Post-Doctoral Researcher of Radiobiology and a resident in Radiology at the Bundeswehr Institute of Radiobiology, Munich, Germany.

Simone Schüle

Simone Schüle, MD, is a Post-Doctoral Researcher of Radiobiology and a resident in Radiology at the Bundeswehr Institute of Radiobiology, Munich, Germany.

Reinhard Ullmann

Reinhard Ullmann, PhD, is a biologist and senior scientist at the Bundeswehr Institute of Radiobiology, Munich, Germany.

Matthias Port

Matthias Port, MD, is a Professor of Radiobiology and Internal Medicine and Head of the Bundeswehr Institute of Radiobiology, Munich, Germany.

Michael Abend

Michael Abend, MD, is a Professor of Radiobiology and Deputy Head of the Bundeswehr Institute of Radiobiology, Munich, Germany.