Ionizing radiation (IR) causes damage to living organisms. The health effects of IR for different total doses and dose rates at which IR was delivered have to be defined by statistical analyses based on whole organism endpoints such as an increase in the risk for development of cancer or an increased risk of life shortening. The factor by which a total dose could be increased, if protracted, for the same final biological effect, is known as dose and dose-rate effectiveness factor (DDREF). The cumulative protracted radiation received by the entire population of USA is very large and falls under regulatory policies that are government defined. These policies rely on the work of national and international agencies evaluating potential dangers of IR using the DDREF value as one of the key input factors for consideration of protracted IR exposures. Ultimately, government regulated limits for occupational and public IR exposures (mostly protracted) and recommendations for X-ray based medical diagnostic procedures (mostly low total doses) all depend on currently accepted DDREF value. Using computational tools and animal data on acute and protracted exposures we found that the DDREF estimate used at this time is inappropriate (Haley et al. 2015) but that dose-rate effectiveness factor (DREF) can be evaluated using extensive animal data. In this project we propose to use interspecies comparisons to refine (1) external beam DREF values and (2) radionuclide dose/quality/route of administration dose rate effectiveness factors (DREF) for specific types of radiation induced cancers (and life shortening from internal emitters). This is especially important in light of the fact that several international bodies are looking to change values for DDREF? a letter from ICRP sent specifically to our group supporting the importance of this work is attached to the application.

Public Health Relevance

Dose and dose-rate effectiveness factor (DDREF) is factor used for regulation of occupational and public radiation exposure limits for protracted exposures. By using an extensive animal dataset that enables direct comparison of protracted and acute radiation exposures, and developing suitable computational tools we found that the current DDREF estimate is inappropriate (Haley et al. 2015), but that a dose-rate effectiveness factor (DREF) evaluation is feasible. We propose to refine DREF values for life-shortening and cancers; this work is also of interest to the International Commission on Radiological Protection (ICRP) (letter attached).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA221150-04
Application #
9980304
Study Section
Radiation Therapeutics and Biology Study Section (RTB)
Program Officer
Prasanna, Pat G
Project Start
2017-08-16
Project End
2022-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
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Paunesku, Tatjana; Woloschak, Gayle (2018) Reflections on Basic Science Studies Involving Low Doses of Ionizing Radiation. Health Phys 115:623-627
Paunesku, Tatjana; Woloschak, Gayle E (2017) Future Directions of Intraoperative Radiation Therapy: A Brief Review. Front Oncol 7:300
Held, Kathryn D; Woloschak, Gayle E (2016) NCRP Program Area Committee 1: Basic Criteria, Epidemiology, Radiobiology and Risk. Health Phys 110:98-100