Continuous external Co-60 gamma-ray exposure, at various dose rates, terminated at various total doses

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From 1968 to 1977 Bill Norris and Tom Fritz performed one of several Beagle Dog Experiments at Argonne National Laboratory. They exposed dogs to 22 h/d external cobalt-60 gamma-ray, at various dose rates, terminated at various total doses in order to investigate the effect of total dose and dose rate in beagles given protracted whole-body cobalt-60 gamma ray exposure to: (1)provide a basis of comparison for beagles given continuous irradiation (103.05), (2) complement research on mice at ANL, and (3) address practical issues in radiation health hazards in man.

Contents

Red Book Description

Results as of 1987:

Dose Rate (rad/day) Total Dose (rad) No. of animals No. of animals Dead Mean survival of dead animals (years) Mean survival of living animals (years) Fatal Tumors (%)* Myeloproliferative Disorder (%)
None 0 86 66 11.4 12.4 28 (42) 0 (0)
3.8 450 20 10 10.3 12.1 5 (50) 0 (0)
3.8 1050 24 24 10.7 14 (58) 0 (0)
3.8 1500 20 19 10.2 13.6 13 (68) 1 (5)
7.5 450 20 10 10.4 12.4 8 (80) 1 (10)
7.5 1050 24 23 10.2 13.1 14 (61) 0 (0)
7.5 1500 19 19 9.0 15 (79) 2 (11)
7.5 3000 20 20 7.8 16 (80) 3 (15)
12.8 450 20 10 10.7 12.2 7 (70) 0 (0)
12.8 1050 21 17 10.0 13.3 10 (59) 0 (0)
12.8 1500 19 15 9.2 11.7 8 (53) 1 (7)
12.8 3000 10 10 10.6 7 (70) 0 (0)
26.3 450 20 10 8.0 11.8 4 (40) 0 (0)
26.3 1050 20 20 10.1 12 (60) 0 (0)
  • including Myeloproliferative Disorders

This experiment complements the preceding continuous lifetime-irradiation experiment. Dogs were irradiated 22 hours per day, 7 days per week, in a specially constructed facility (Grahn, 1986; Norris, 1976). Particular attention was given to dosimetry; all factors contributing to the dose rate and total dose were normalized in the irradiation field by migrating dogs through all positions and orientations with respect to the irradiation source. Dose rates shown above are average absorbed dose; doses in air were quoted in early publications. Dogs listed above include only those surviving 100 days following termination of exposure.

Several papers have been published describing the then-current status of this study (Fritz, 1978, 1986; Grahn, 1986; Seed, 1985). The partial results have been employed in modeling the leukemogenic process (Seed, 1985, 1987, 1987b; Tolle, 1979b). A detailed account has appeared of an acute monocytic leukemia in a dog from this study (Tolle, 1979).

Interim conclusions drawn from this experiment include the following: l)There is a positive trend in the proportions of dogs dying of tumors as total dose is increased at all dose rates; there is no indication of a dose-rate effect except at a total dose of 3000 rad, where the trend is negative. 2) The timing of deaths in all irradiated groups differs from the control group, except for the 450 rad total dose group where meaningful analysis is not yet possible. 3) Only total dose influences the timing of fatal tumors, but neither total dose nor dose rate influences the timing of nontumor deaths. 4) Although a significant increase in myeloproliferative disorders is observed, it is smaller than observed in dogs irradiated continuously; dogs appear to recover from hematopoietic damage after irradiation is terminated, and die at later times of soft tissue malignancies(Fritz, 1986; Seed, 1985).

Information relevant to this experiment will be found in the following Argonne National Laboratory periodic reports:

  • 1971 (Dec) ANL-7870 138-1 45
  • 1972 (Dec) ANL-7970 192-203
  • 1973 (Dec) ANL-8070 31-54
  • 1974 (Dec) ANL-75-30 9-14
  • 1975 (Dec) ANL-76-99 10-19
  • 1976 (Dec) ANL-77-55 34-40
  • 1977 (Dec) ANL-78-90 78-86
  • 1978 (Dec) ANL-79-90 6-12
  • 1980 (Dec) ANL-80-90 8-13
  • 1981 (Aug) ANL-81-50 8-13
  • 1982 (Jun) ANL-82-35 11-19
  • 1983 (May) ANL-83-40 27-36
  • 1984 (Aug) ANL-84-30 37-46
  • 1985 (Aug) ANL-85-30 63-72

Copied from: Roy C Thompson. Life-Span Effects of Ionizing Radiation in the Beagle Dog (1989) (link pdf)


Gray Book Description

Institution: Argonne National Laboratory, Argonne IL

Scientists: Bill Norris; retired, Tom Fritz; retired

Purpose Investigate the effect of total dose and dose rate in beagles given protracted whole-body cobalt-60 gamma ray exposure to: (1)provide a basis of comparison for beagles given continuous irradiation (103.05), (2) complement research on mice at ANL, and (3) address practical issues in radiation health hazards in man.

Status Exposure initiated between 1968 and 1978, death of last dog at ANL in 1991.

Treatment External cobalt-60 gamma-ray exposure, 22 h/d, at various dose rates, terminated at various total doses. Dogs were irradiated 22 h/d, 7 d/w, in a specially constructed facility. Particular attention was given to dosimetry; all factors contributing to the dose rate and total dose were normalized in the irradiation field by migrating dogs through all positions and orientations with respect to the irradiation source. Control dogs were similarly housed in cages and migrated through positions in the control animal room.

Dosimetry: Radiation was delivered with a cobalt-60 gamma beam apparatus equipped with steel attenuators which were changed every few mo to compensate for radioactive decay. Beagles were caged singly in two-tiered fiberglass cages placed at calculated distances from the source; cages were rotated daily to compensate for the propensity of the dog to occupy the rear of the cage. Dose rate at the center of the cage was measured and converted to absorbed dose.

Endpoints Dogs were provided with life-time clinical care, including annual physical examination and blood work-ups. At necropsy, a thorough gross examination was conducted, ant a preliminary cause of death was determined. After histopathological examination of tissues from suspected lesions and an extensive suite of representative tissues, a "final" cause of death was determined and entered into the database.

Animal 257 Beagle dogs (118 females 139 males), mean age 490 d, in 14 groups, plus 86 age matched dogs from the colony controls. Constraints on the availability of space in the irradiation facility resulted in a range in age at initiation of exposure from 368 to 756 d.

Results Hazard models indicated that the probability of acute death (related to hematopoietic aplasia) was positively associated with total dose and dose rate. Once a dog survived the initial hematopoietic effects of irradiation, the risk of death from causes other than cancer, while elevated, was far less responsive than the neoplastic end points. No relationship between tumor or chronic nontumor deaths and dose rate could be identified. However, survival curves for tumor mortality did separate into a pattern clearly dependent on accumulated dose.

References Carnes, B.A. and T.E. Fritz. Responses of the beagle to protracted irradiation. I. Effect of total dose and dose rate. Radiation Research 128 125-132, 1991.

Experimental Groups Study 103.05 Life-Span Health Risks: Duration-of-Life Gamma-Irradiation of Young Adult Beagles

Group Id Dose Rate (mGy/d) Day of Exposure Total Dose (rad) Number of Dogs
01 caged controls 0 0 86
02 38 118 450 20
03 38 276 1050 24
04 38 395 1500 20
05 75 60 450 20
06 75 140 1050 24
07 75 200 1500 19
08 75 400 3000 20
09 128 35 450 20
10 128 82 1050 21
11 128 117 1500 19
12 128 234 3000 10
13 263 17 450 20
14 263 40 1050 20
Total 343


Copied from: GB Gerber, CR Watson, T Sugahara, and S Okada. International Radiobiology Archives of Long-Term Animal Studies I. Descriptions of Participating Institutions and Studies (1996) ([1])


Data

Data from this study is available freely from the Beagle Dog archive at northwestern [2] and from the European Radiobiology Archive [3] ( password required ).

Tissues

Tissues preserved from these studies are stored at the Beagle Dog Archive at Northwestern University. Tissues may be searched for using their website [4].

References

  • Grahn D. and Fritz T.E. 1986. Chronic radiation injury with mice and dogs exposed to external whole-body irradiation at the Argonne National Laboratory. In Life-Span Radiation Effects Studies in Animals: What Can They Tell Us? (R.C. Thompson and J.A. Mahaffey, eds., CONF-830951, NTIS, Springfield, VA) 14-31.
  • Norris W.P., Tyler S.A. and Sacher G.A. 1976. An interspecies comparison of responses of mice and dogs to continuous gamma irradiation. In Biological and Environmental Effects of Low-Level Radiation. Vol. 1 (International Atomic Energy Agency, Vienna) 147-1 56.
  • Fritz, 1978, Fritz T.E., Norris W.P., Tolle D.V., Seed T.M., Poole C.M., Lombard L.S. and Doyle D.E. 1978. Relationship of dose rate and total dose to responses of continuously irradiated beagles. In Late Biological Effects of Ionizing Radiation, Vol.11 (International Atomic Energy Agency, Vienna) 71-82. pdf
  • Fritz T.E., Seed T.M., Tolle D.V. and Lombard L.S. 1986. Late effects of protracted whole-body irradiation of beagles by cobalt-60 gamma rays. In Life-Span Radiation Effects Studies in Aninzals: What Can They Tell Us? (R.C. Thompson and J.A. Mahaffey, eds., CONF-830951, NTIS, Springfield, VA) 116-141.
  • Seed T.M., Kaspar L.V., Fritz T.E. and Tolle D.V. 1985. Cellular responses in chronic radiation leukemogenesis. In Carcinogenesis, Vol. 10 (E. Huberman and S.H. Barr, eds., Raven Press, New York) 363-379.
  • Seed T.M., Chubb G.T., Tolle D.V., Fritz T.E., Poole C.M., Doyle D.E., Lombard L.S. and Kaspar L.V. 1983. The ultrastructure of radiation-induced endosteal myelofibrosis in the dog. In Scanning Electron Microscopy1 1982/1. (O.Johari, et al., eds., SEM Inc., AMF O'Hare, Chicago) 377-391. pubmed
  • Seed T.M. 1987b. Structure-function relationships in radiation-induced cell and tissue lesions: Special references to the contributions of scanning electron microscopy and hematopoietic tissue responses. Scanning Microsc. 1 :255-272. abstract
  • Tolle D.V., Seed T.M., Fritz T.E. and Norris W.P. 1979b. Irradiation- induced canine leukemia: A proposed new model. Incidence and Hematopathology. In Experimental Hematology Today 1979. (S.J. Baum and G.D. Ledney, eds., Springer-Verlag, New York) 247-256.
  • Tolle D.V., Seed T.M., Fritz T.E., Lombard L.S., Poole C.M. and Norris W.P. 1979. Acute monocytic leukemia in an irradiated beagle. Vet. Pathol. 16:243-254. pubmed
  • Carnes, B.A. and T.E. Fritz. Responses of the beagle to protracted irradiation. I. Effect of total dose and dose rate. Radiation Research 128 125-132, 1991. jstor
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