Past and Future Work on Radiobiology Mega-Studies: A Case Study at Argonne National Laboratory

Abstract

Between 1952 and 1992 more than 200 large radiobiology studies were conducted in research institutes throughout Europe, North America and Japan to determine the effects of external irradiation and internal emitters on the life span and tissue toxicity development in animals. At Argonne National Laboratory, 22 external beam studies were conducted on nearly 700 beagle dogs and 50,000 mice between 1969 and 1992. These studies helped to characterize the effects of neutron and gamma irradiation on lifespan, tumorigenesis, and mutagenesis across a range of doses and dosing patterns. The records and tissues collected at Argonne during that time period have been carefully preserved and redisseminated. Using these archived data ongoing statistical work has been done and continues to characterize quality of radiation, dose, dose rate, tissue, and gender specific differences in the radiation responses of exposed animals. The ongoing application of newly developed molecular biology techniques to the archived tissues has revealed gene specific mutation rates following exposure to ionizing irradiation. The original and ongoing work with this tissue archive is presented here as a case study of a more general trend in the radiobiology mega studies. These experiments helped form the modern understanding of radiation responses in animals, and continue to inform development of new radiation models. Recent archival efforts have facilitated open access to the data and materials produced by these studies and so a unique opportunity exists to expand this continued research.

X-Ray Fluorescence Microscopy for Investigation of Archival Tissues

“…Especially in prostate cancer distribution of Zn is considered to be a valuable diagnostic marker. Zinc concentration differences between prostate and testis tissue were several-fold, as expected (Barrea et al, 2010, Haley et al, 2011). Additionally, in prostate it was possible to segregate the prostate gland tissue from connective tissue by comparing zinc concentrations and distribution patterns (Figure 1).…”

“…In the USA, several national laboratories, institutes and universities were active in this type of research as well; especially Argonne National Laboratory, Oakridge National Laboratory, Pacific Northwest National Laboratory, University of Davies California, Lovelace Respiratory Research Institute and others. Studies at Argonne National Laboratories (ANL) between 1969 and 1992, included nearly 700 beagles and 50,000 mice (Haley et al 2011). These studies aimed to understand the effects of neutron and Cobalt-60 gamma-ray irradiation on lifespan and tumorigenesis across a wide range of dose and dosing patterns.…”

The Effects of Radiation and Dose-Fractionation on Cancer and Non-Tumor Disease Development

“…This analysis utilized historical data from the previously described Janus database [14]. Each observation in the database was associated with a radiation dose, fractionation, and quality, expressed as irradiation codes (specific dose values are also available), lifespan, date of first dose, proctor (pathologist) who performed the necropsy, as well as observed pathologies (the probable cause of death and accompanying diseases).…”

“…This dataset, which is currently hosted at Northwestern University (), is publically available, and presents a unique opportunity to explore the effects of radiation on animals (at a scale no longer considered feasible by today’s standards) in a controlled environment and under experimental conditions with a radiation source that is no longer available. Although some recent studies examining the Janus database [13] have aimed to re-discover and preserve this and other large scale radiation experiments [14,15], this manuscript is a result of a new effort to re-visit and analyze the data on mice exposed to total doses in the range of clinical exposures either acutely or in 60 fractions. Previous studies using this database either focused on the tumorigenic effects of radiation [16,17], or examined pathologies at lower total doses of radiation, comparing frequencies of disease between groups of control and irradiated animals [18].…”

Low Dose Effects

“…Studies from the Janus archives (janus.northwestern.edu/wololab) were analyzed that included animals from the large-scale studies carried out by the U.S. Department of Energy in the 1950-80s (Haley et al 2011). Of the 452,595 animals in the European and Janus archives, two major studies carried out in the 1980s and 1990s using approximately 400 mice documented hormetic effects of radiation (Covelli et al 1984(Covelli et al , 1988Maisin et al 1983Maisin et al , 1996Maisin et al , 1988.…”