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2017ASTRO RADIATION/CANCER BIOLOGY PRACTICE EXAMINATION AND STUDY GUIDE Produced by the Radiation/Cancer Biology Practice Examination and Study Guide Taskforce of American Society for Radiation Oncology Copyright © 2017 American Society for Radiation Oncology Please address all correspondence to: Christopher Barker, MD, Assistant Member Department of Radiation Oncology Memorial Sloan-Kettering Cancer Center 1275 York Avenue New York, NY 10065 Tel: 212-639-8168 Email: [email protected] Gayle Woloschak, PhD, Professor Departments of Radiation Oncology and Radiology Robert E. Lurie Comprehensive Cancer Center Feinberg School of Medicine Northwestern University 303 E. Chicago Avenue, Ward 13-002 Chicago, IL 60611 Tel: 312-503-4312 Email: [email protected] 1 Editors-in-Chief (2014) Gayle E. Woloschak, Ph.D. Northwestern University Medical School Christopher Barker, M.D. Memorial Sloan Kettering Cancer Center Editor-in-Chief (2006-2012) Barry S. Rosenstein, Ph.D. Mount Sinai School of Medicine NYU School of Medicine Associate Editors (2013) Elizabeth Balcer-Kubiczek, Ph.D. Juong G. Rhee, Ph.D. University of Maryland School of Medicine University of Maryland School of Medicine Beth Beadle, M. D., Ph.D. Navesh K. Sharma, Ph.D., D.O. University of Univ. Texas M. D. Anderson Cancer Center Maryland School of Medicine Eleanor Blakely, Ph. D. Zhiyuan Shen, M.D., Ph.D. UMDNJ-Robert Wood Lawrence Berkely National Laboratory Johnson Medical School David Gius, M. D., Ph. D. Michael D. Story, Ph.D. University of Texas Northwestern University Medical School Southwestern Medical Center Martin Hauer-Jensen, Ph. D. Phuoc Tran, M. D., Ph. D. Johns Hopkins School of Univ. Arkansas School of Medicine Medicine Michael Joiner, Ph. D. Brian Marples, Ph. D. William Beaumont Hospital Wayne State University Associate Editors (2011-2012) Elizabeth Balcer-Kubiczek, Ph.D. William Beaumont Hospital University of Maryland School of Medicine Christopher Barker, M.D. Memorial Sloan Kettering Cancer Center Michael C. Joiner, Ph.D. Karmanos Cancer Institute, Wayne State University School of Medicine David G. Kirsch, M.D., Ph.D. Duke University Medical Center Brian Marples, Ph.D. 2 Michael E.C. Robbins, Ph.D. Wake Forest University School of Medicine Juong G. Rhee Ph.D. University of Maryland School of Medicine Navesh K. Sharma, Ph.D., D.O. University of Maryland School of Medicine Zhiyuan Shen, M.D., Ph.D. UMDNJ-Robert Wood Johnson Medical School Michael D. Story, Ph.D. University of Texas Southwestern Medical Center 3 Gayle E. Woloschak, Ph.D. Northwestern Brad G. Wouters, Ph.D. University Medical School Ontario Institute for Cancer Research Associate Editors (2006-2011) Kathryn D. Held, Ph.D. Jacqueline Williams, Ph.D. Harvard Medical School Massachusetts General University of Rochester Medical Center Hospital Elaine M. Zeman, Ph.D. Sara Rockwell, Ph.D. University of North Carolina School of Medicine Yale University School of Medicine Contributors Joan Allalunis-Turner, Ph.D. David Kirsch, M.D., Ph.D. Cross Cancer Institute Duke University School of Medicine Sally A. Amundson, Ph.D. Amy Kronenberg, Sc.D. Columbia University Lawrence Berkeley National Laboratory Elizabeth K. Balcer-Kubiczek, Ph.D. William F. Morgan, Ph.D. University of Maryland School of Medicine Pacific Notrhwest National Laboratory Kevin A. Camphausen, M.D. John P. Murnane, Ph.D. National Cancer Institute/NIH University of California, San Francisco Theodore L. DeWeese, M.D. Johns Hopkins Peggy L. Olive, Ph.D. University School of Medicine British Columbia Cancer Research Centre Evan B. Douple, Ph.D. The National Academies Martin Pruschy, Ph.D. Nuclear and Radiation Studies Board University Hospital Zurich Adriana Haimovitz-Friedman, Ph.D. Memorial Sloan- Sara Rockwell, Ph.D. Kettering Cancer Center Yale University School of Medicine Dennis E. Hallahan, M.D. Michael E.C. Robbins, Ph.D. Vanderbilt University Wake Forest University School of Medicine Martin Hauer-Jensen, M.D., Ph.D. Joseph L. Roti Roti, Ph.D. University of Arkansas for Medical Sciences Washington University School of Medicine Kathryn D. Held, Ph.D. Carolyn I. Sartor, M.D. Harvard Medical School Massachusetts General University of North Carolina School of Medicine Hospital Joann Sweasy, Ph.D. Richard P. Hill, Ph.D. Yale University School of Medicine Ontario Cancer Institute Marie-Catherine Vozenin-Brotons Ph.D. Rakesh K. Jain, Ph.D. Harvard Medical School Institut Gustave Roussy Massachusetts General Hospital Gayle E. Woloschak, Ph.D. Northwestern University Medical School 4 Henning Willers, M.D. Elaine M. Zeman, Ph.D. Harvard Medical School Massachusetts General University of North Carolina School of Medicine Hospital Daniel Zips, Ph.D. Jacqueline Williams, Ph.D. Technical University Dresde University of Rochester Medical Center 5 Table of Contents Table of Contents ............................................................................................................................. 5 Radiation-Matter Interactions ......................................................................................................... 7 DNA Damage Mechanisms ............................................................................................................. 10 DNA Repair Mechanisms ................................................................................................................ 11 Chromosome Damage .................................................................................................................... 14 Cell Death Mechanisms .................................................................................................................. 16 Survival Assay ................................................................................................................................. 19 Cell Survival Models ....................................................................................................................... 21 Linear Energy Transfer ................................................................................................................... 24 Oxygen Effect ................................................................................................................................. 26 Cellular Repair ................................................................................................................................ 28 Tumor Assay Systems ..................................................................................................................... 30 Microenvironment ......................................................................................................................... 32 Cell and Tissue Kinetics .................................................................................................................. 35 Molecular Signaling ........................................................................................................................ 39 Cancer ............................................................................................................................................ 41 Total Body Irradiation .................................................................................................................... 45 Normal Tissue Response ................................................................................................................ 47 Therapeutic Ratio ........................................................................................................................... 53 Time, Dose, Fractionation .............................................................................................................. 55 Brachytherapy ................................................................................................................................ 57 Alternative Delivery Systems.......................................................................................................... 58 Chemotherapy................................................................................................................................ 60 Radiation Modifying Drugs ............................................................................................................. 63 Hyperthermia ................................................................................................................................. 66 Radiation Carcinogenesis ............................................................................................................... 67 Heritable Effects ............................................................................................................................. 69 Embryonic Effects .......................................................................................................................... 70 Radiation Protection ...................................................................................................................... 71 Molecular Techniques .................................................................................................................... 72 Molecular Imaging ......................................................................................................................... 74 ANSWER KEY .................................................................................................................................. 75 Radiation-Matter Interactions ....................................................................................................... 76 DNA Damage Mechanisms ............................................................................................................
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