Woloschak Lab Feinberg School of Medicine, Radiation Oncology

HISTORY

The University of California at Davis lab went through several lab changes under the School of Veterinary Medicine: “Radiobiology Laboratory”, and the “Laboratory for Energy-Related Health Research” (LEHR) during the Beagle studies years.

There are several different accounts of when the first studies began as reported in annual reports and historical documents, with most annual reports stating that the X-ray or irradiation studies began in 1951 (1989, 1968 annual reports) and some archive sources stating 1952. Davis also reports that the 90-Sr studies began in 1956 – where as the NRA reports this start date as 1961 – for the year the dogs were first exposed to the radionuclide as reported in the data.  There are various theories for these dates, such as for the date of signing the financial contract, and or  testing dates in competition to other labs. We offer the dates with the annual reports, and literature pdf’s for you to gain further understanding into these alterations. 

The Irradiation Study, or X ray studies also called “Project 4” began in 1951 with a contract with AEC Atomic Energy Commission. The X ray study, or “Project 4” focused on tumor induction and lifespan shortening after acute exposure. In 1956 they added strontium (90-Sr) “Project 6”, with the parallel 226-Ra studies also called life-span dog experiments. The 226-Ra study, part of “Project 6”, was designed to simulate the exposure pattern of the human dial painters. The Strontium study was used to evaluate the health risk from fallout of 90-Sr. The Department of Energy supported the laboratory studies through 1992; biological specimens and research records were transferred to the National Radiobiology Archives in 1990.

University of California, Davis, School of Veterinary Medicine, Radiobiology Laboratory recorded dates for studies:

1989 Annual Report

• 1951 X-ray Studies
• 1956 90-Sr and 226-Ra Studies reported by Leon Rosenblatt, Biostatician and lead PI
• 1957 90-Sr and 226-Ra Studies reported by Otto G. Raabe, Director

1968 Annual Report

• 1951 X-irradiation Study to simulate radiation of aircraft propelled by nuclear energy.
• 1956 90-Sr ingestion and 226-Ra Studies

1958 Annual Report (earliest accessible annual report currently).

• No initial dates given.
• 1957 X-ray studies concluded and Maxitron unit used in experiment was condemned.
• 1954 131-Iodine injection study

International Radiobiology Archives of Long-Term Animal Studies and Thompson’s Life-span effects of ionizing radiation in the Beagle dog: 

• 1952-1958 Single or Fractionated X-irradiation of Young Adult Female Beagles. 
• 1961 90-Sr ingested 
• 1963 90-Sr injected and 226-Ra

Laboratory directors:

Other investigators associated with the Davis studies were (in alphabetic order): S.A. Book, G.R. Cain, M.R. Culbertson, R.J. Della Rosa, T.G. Kawakami, A.K. Klein, D.H. McKelvie, M.H. Momeni, J.P. Morgan, N.J. Parks, R.R. Pool, Leon Rosenblatt, W.L. Spangler, and, F.D. Wilson. 

Access the full history written by Principal Investigator (formerly Biostatician) Leon Rosenblatt, taken from the UC Davis 1989 Annual Technical Report.

References

Experimental Categories of Davis Subjects 

• X-ray studies (no alpha prefix for numerical ID) (1952 -1958)
• “D” dogs received dietary 90-SR  (1961 – 1967)
• “R” dogs received injected 226-Ra  (1963 -1967)
• “S” dogs received injected 90-Sr  (1965-1983)
• “C” dogs in Cobalt studies (1971 – 74)

X-Irradiation Studies

Single or fractionated x-irradiation studies, sometimes referred to as Project 4, involving 352 females received first exposures at 8-15 mo. old to study lifespan and tumor risks.  All subjects were noted to have life shortening in comparison to the controls after treatment of bilateral, 250 kVX-ray exposures at different intervals.

“D” Dogs

In the D-series, 90SrC12 was fed to pregnant [dogs] beginning at the start of the second trimester of gestation, at the initiation of fetal ossification.  The pups nursed their mothers, who were still on dietary 90Sr, and were weaned at 42 days of age.  The mothers were removed, and the pups remained on 90Sr until they were 540 days old. At 570 days they were transferred to outdoor kennels.

Purpose: This study was initiated in response to the concern for possible long-term human health effects from strontium-90 in the fallout from tests of nuclear weapons. Beagles were the surrogate for humans as their life was relatively long and receive the radiation in similar form to what humans would in their food supply. 

Study:  Life-Span Health Risks: Daily Ingestion of Strontium-90 in Immature (Fetal to 540-Day-Old) Beagles. 1961 – 1969 with death of last dog in 1986. Final papers written, and information and specimens transferred to NRA in 1990. 

483 Beagle dogs (239 female: 244 male) in eleven groups. 

Results: Skeletal uptake averaged 2% of the administered dose Daily dose rate to the skeleton Declined slowly to about 45% of peak value late in life. The time-weighted average dose rate for fed Sr-90 and injected Ra-226 was a robuse measure that declined from peak values only about 20% late in life. A threshold like response was observed: no sarcomas were observed in the lowest three dose groups, but the number of primary bone sarcomas increased rapidly in the higher dose groups. The primary sarcomas, 49 were osteosarcomas, which occured primarily in the higher dose groups. The ratio of appendicular to axial sarcomas was 40:26. The distribution of sarcoma among 16 bone groups was correlated with the distribution of cancellous bone volume-to-surface ratio and not with either skeletal mass or dose distribution. 

“R” Dogs

The R-dogs received 8 equal intravenous injections of 226-Ra in a nitric acid- saline carrier, beginning at 435 days of age and ending at 540 days of age. They, too, went outside at 570 days.

“S” Dogs

The S-dogs got a single intravenous injection of 90-SrC12 at 540 days and were also transferred to the outdoor facility at 570 days.  The 30-day interval was used to allow the dogs to eliminate as much of their radionuclidic burden as possible while they were still indoors.

Purpose: This study supplemented the Sr-90 chronic feeding study (102.02) providing a comparison of single and repeated administration, and also serving as a link to the more extensive single injection study ( Utah 101.05). 

Study:  Life-Span Health Risks: Single Injection of Strontium-90 in Young Adult Beagles 102.03. This study took place between 1965-1969, death of last og in 1983. Final papers written, information and specimens transferred to the NRA in 1990. 
45 Beagles dogs (25 female; 20 male), 540 d old, in 3 groups.

Results:  Skeletal uptake was about 33% of administered dose. Daily dose to the skeleton fell rapidly after injection and declined to about 10% of pead values late in life. For more extensive information see page 161 of Thompson’s “Life-Span Effects of Ionizing Radiation in the Beagle Dog.” 

“C” Cobalt Studies

During the 1970’s around 222 beagles were exposed to Cobalt-60 from an outdoor irradiator facility field to study the effects of gamma rays. The dogs in these studies wore collars outfitted with dosimeters measuring the exposure each dog recieved in the field study. 

There were twelve groups of varying exposures studied.

References:

1989 Annual Technical Report

Gerber, G B, Watson, C R, Sugahara, T, & Okada, S. International radiobiology archives of long-term animal studies. I. Descriptions of participating institutions and studies. United States. https://doi.org/10.2172/376402 

DATA

In December 1990 Chuck Watson and Sean Smith, of National Radiobiology Archive,  visited the Laboratory forEnergy-Related Health Research (LEHR) at UC DAVIS. While they were there, Chuck Watson and Cliff Burton (Database Administrator at LEHR) documented the LEHR SQL Database. Most of the LEHR specific documentation in this document is from that time period. Cliff exported the Data General SQL database to ASCII 9-track tape files having fixed-widthrecords and also having double quotation marks delimiting the fields and separating the fields. When Chuck and Sean returned to PNL with the 9-track tape, the database tape files were copied to their MicroVax II mini. The database files were nextcopied to a DOS formatted rewritable optical cartridge. Shairylann McIntyre and Sean Smith then prepared the files for a Paradox import using WordPerfect 5.1’s text editing capabilities. After the files were transformed into Paradox tables, modifications were made to the table structures to allow for easy linkage with the NRA Summary Database.

Most of these data files were given to the Woloschak lab in the form of the optical cartridge and a zipfile. We offer the following excel tables extracted from these datasets.

The table below are designed to be relational within a database.

Database Documentation Files:

Davis Specific Tables: Database Documentation Details: Davis3-W51tables

Davis Specific Tables: Davis2 Paradox codes