title: Induction of osteosarcoma and acute myeloid leukaemia in CBA/H mice by the alpha-emitting nuclides, uranium-233, plutonium-239 and amercium-241.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: National Radiological Protection Board, Didcot, Oxon, UK. michele.ellender@nrpb.org.uk
authors.forename: M
authors.initials: M
authors.lastname: Ellender
authors.forename: J D
authors.initials: JD
authors.lastname: Harrison
authors.forename: H
authors.initials: H
authors.lastname: Pottinger
authors.forename: J M
authors.initials: JM
authors.lastname: Thomas
mesh_terms: D000576:Americium / Q000009:adverse effects*; D000818:Animals; D001842:Bone and Bones / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015470:Leukemia, Myeloid, Acute / Q000209:etiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D012516:Osteosarcoma / Q000209:etiology*; D011005:Plutonium / Q000009:adverse effects*; D011868:Radioisotopes / Q000009:adverse effects*; D012044:Regression Analysis; D013997:Time Factors; D014018:Tissue Distribution; D014501:Uranium / Q000009:adverse effects*
chemical_list: D011868:Radioisotopes; D014501:Uranium; D011005:Plutonium; D000576:Americium