Reference SummaryEllender M, Int J Radiat Biol 2001 Jan;77(1):41-52

Title

Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.

Authors

Ellender M; Harrison JD; Pottinger H; Thomas JM

Journal

Int J Radiat Biol

Volume

77

Issue

1

Year

2001

Pages

41-52

Abstract

PURPOSE: To compare tumour induction in CBA/H mice, principally osteosarcoma and acute myeloid leukaemia, resulting from exposure to the alpha-emitting nuclides, uranium-233, plutonium-239 and americium-241, and to relate differences between the three nuclides to the pattern of dose delivery within tissues. MATERIALS AND METHODS: Each nuclide was administered intraperitoneally in citrate solution to three groups of adult male CBA/H mice at levels of activity which gave estimated life-time average skeletal doses of about 0.25-0.3 Gy, 0.5-1 Gy and 1-2 Gy. Animals were carefully monitored and sacrificed as soon as they showed signs of ill health; tumours were identified by standard histopathological techniques. RESULTS: Statistical modelling by Cox regression showed that, considering all three nuclides together, there was a highly significant increase in risk of death from osteosarcoma or myeloid leukaemia with increasing dose rate. For osteosarcoma, the effect was significantly greater for 239Pu than 241Am, while separate analysis for 233U showed no significant increase with increasing dose rate. For example, the increase in relative risk of death from osteosarcoma for an increase in life-time average dose rate to bone of 1 mGyd(-1) was 4.2 (2.7-6.5) for 239Pu, 2.3 (1.4-3.4) for 241Am and 1.1 (0.4-3.1) for 233U. For myeloid leukaemia, there was no significant difference between 239Pu and 241Am in the effect of dose rate. The increase in relative risk from myeloid leukaemia for an increase in average dose rate of 1 mGyd(-1) was 1.8 (1.1-2.8) for 239Pu, 2.0 (1.4-2.9) for 241Am and 1.5 (0.8-2.7) for 233U. Significant increases in renal and hepatic carcinomas were also recorded in animals exposed to 233U and 241Am, respectively. Studies of the distribution of the nuclides within the skeleton, published separately, have shown differences in their retention in individual bones and within bone. The proportions of decays occurring near to endosteal bone surfaces and throughout bone marrow were in the order: 239Pu> 241Am>233U. CONCLUSIONS: For osteosarcoma, the relative effectiveness of the nuclides in terms of average bone dose, in the order 239Pu>241Am>233U, is consistent with the proportion of dose delivered near to endosteal surfaces. For myeloid leukaemia, the greater effectiveness of 239Pu and 241Am than 233U is consistent with their accumulation in marrow.

Links

J:67447 – MGI References
11213349 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/Do "albino mice"

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CBA/H Adrenal gland - Cortex adenoma
  • (see notes)
Adrenal gland - Cortex

observed

CBA/H Adrenal gland - Medulla pheochromocytoma
  • (see notes)
Adrenal gland - Medulla

observed

CBA/H Blood vessel hemangioma
  • (see notes)
Bone

observed

CBA/H Blood vessel hemangioma
  • (see notes)
Blood vessel

observed

CBA/H Blood vessel hemangiosarcoma
  • (see notes)
Bone

observed

CBA/H Blood vessel hemangiosarcoma
  • (see notes)
Blood vessel

observed

CBA/H Bone osteoma
  • (see notes)
Bone

observed

CBA/H Bone osteosarcoma Bone

2.3

CBA/H Bone osteosarcoma
  • uranium-233
Bone

1.9 - 2.2

CBA/H Bone osteosarcoma
  • plutonium-239
Bone

2.1 - 30

CBA/H Bone osteosarcoma
  • americium-241
Bone

0 - 45

ICR Bone osteosarcoma
  • plutonium-239
Bone

2.0 - 10

CF-1 Bone osteosarcoma
  • plutonium-239
Bone

4.0 - 10

CF-1 Bone osteosarcoma
  • uranium-233
Bone

1.0 - 31

C57BL/Do Bone osteosarcoma
  • plutonium-239
Bone

0 - 27

CBA/H Kidney - Renal tubule adenoma Kidney - Renal tubule

2.3

CBA/H Kidney - Renal tubule adenoma
  • uranium-233
Kidney - Renal tubule

0 - 2.1

CBA/H Kidney - Renal tubule adenoma
  • plutonium-239
Kidney - Renal tubule

0 - 1.0

CBA/H Kidney - Renal tubule adenoma
  • americium-241
Kidney - Renal tubule

0 - 2.1

CBA/H Kidney - Renal tubule carcinoma Kidney - Renal tubule

1.1

CBA/H Kidney - Renal tubule carcinoma
  • uranium-233
Kidney - Renal tubule

4.4 - 15

CBA/H Kidney - Renal tubule carcinoma
  • plutonium-239
Kidney - Renal tubule

3.2 - 4.1

CBA/H Kidney - Renal tubule carcinoma
  • americium-241
Kidney - Renal tubule

0 - 6.25

CBA/H Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • (see notes)
Leukocyte - Monocyte - Macrophage - Histiocyte

observed

CBA/H Leukocyte - Myelocyte (Granulocyte) - Basophil - Mast cell mastocytoma
  • (see notes)
Bone

observed

CBA/H Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic Leukocyte - Myelocyte (Granulocyte)

0

CBA/H Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • uranium-233
Leukocyte - Myelocyte (Granulocyte)

3.7 - 4.4

CBA/H Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • plutonium-239
Leukocyte - Myelocyte (Granulocyte)

4.1 - 8.9

CBA/H Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • americium-241
Leukocyte - Myelocyte (Granulocyte)

4.3 - 10

CBA/H Leukocyte lymphoma Leukocyte

1.1

CBA/H Leukocyte lymphoma
  • uranium-233
Leukocyte

0 - 4.2

CBA/H Leukocyte lymphoma
  • plutonium-239
Leukocyte

3.2 - 9.1

CBA/H Leukocyte lymphoma
  • americium-241
Leukocyte

0 - 5.4

CBA/H Liver blastoma Liver

0

CBA/H Liver blastoma
  • uranium-233
Liver

0 - 1.9

CBA/H Liver blastoma
  • plutonium-239
Liver

0 - 1.0

CBA/H Liver blastoma
  • americium-241
Liver

0

CBA/H Liver hepatocellular adenoma Liver

53

CBA/H Liver hepatocellular adenoma
  • uranium-233
Liver

35 - 38

CBA/H Liver hepatocellular adenoma
  • plutonium-239
Liver

61 - 71

CBA/H Liver hepatocellular adenoma
  • americium-241
Liver

35 - 65

CBA/H Liver hepatocellular carcinoma Liver

43

CBA/H Liver hepatocellular carcinoma
  • uranium-233
Liver

54 - 57

CBA/H Liver hepatocellular carcinoma
  • plutonium-239
Liver

57 - 78

CBA/H Liver hepatocellular carcinoma
  • americium-241
Liver

48 - 75

CBA/H Lung adenoma Lung

19

CBA/H Lung adenoma
  • uranium-233
Lung

11 - 19

CBA/H Lung adenoma
  • plutonium-239
Lung

22 - 25

CBA/H Lung adenoma
  • americium-241
Lung

17 - 24

CBA/H Lung carcinoma Lung

15

CBA/H Lung carcinoma
  • uranium-233
Lung

17 - 27

CBA/H Lung carcinoma
  • plutonium-239
Lung

9.7 - 19

CBA/H Lung carcinoma
  • americium-241
Lung

8.3 - 24

CBA/H Mesodermal cell/mesoblast sarcoma
  • (see notes)
Bone

observed

CBA/H Mesodermal cell/mesoblast sarcoma
  • (see notes)
CNS - Meninges

observed

CBA/H Mesodermal cell/mesoblast squamous cell sarcoma
  • (see notes)
Mesodermal cell/mesoblast

observed

CBA/H Muscle - Smooth leiomyosarcoma
  • (see notes)
Muscle - Smooth

observed

CBA/H Muscle - Striated - Skeletal rhabdomyosarcoma
  • (see notes)
Muscle - Striated - Skeletal

observed

CBA/H PNS - Ganglion - Paraganglion paraganglioma
  • (see notes)
PNS - Ganglion - Paraganglion

observed

CBA/H PNS - Schwann cell schwannoma - malignant
  • (see notes)
PNS - Schwann cell

observed

CBA/H Pancreas - Islet of Langerhans adenoma
  • (see notes)
Pancreas - Islet of Langerhans

observed

CBA/H Pancreas - Islet of Langerhans carcinoma
  • (see notes)
Pancreas - Islet of Langerhans

observed

CBA/H Skin - Hair follicle - Basal cell trichoepithelioma
  • (see notes)
Skin - Hair follicle - Basal cell

observed

CBA/H Tooth odontoma
  • (see notes)
Tooth

observed

CBA/H (Unspecified organ) carcinoma - neuroendocrine
  • (see notes)
(Unspecified organ)

observed