title: Tumorigenic target cell regions in bone marrow studied by localized dosimetry of 239Pu, 241Am and 233U in the mouse femur.
abstract: OBJECTIVE
  To study the temporal change in microdistribution of plutonium-239, americium-241 and uranium-233 in the mouse distal femur and to compare and combine calculated radiation doses with those obtained previously for the femoral shaft. Also, to relate doses to relative risks of osteosarcoma and acute myeloid leukaemia.
  
  
  METHODS
  Computer-based image analysis of neutron-induced and alpha-track autoradiographs of sections of mouse femora was used to quantify the microdistribution of (239)Pu, (241)Am and (233)U from 1 to 448 days after intraperitoneal injection. Localized dose-rates and cumulative doses over this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for doses to the cortical marrow of the femoral shaft. A morphometric analysis of the distal femur was carried out.
  
  
  RESULTS
  Initial deposition on endosteal surfaces and dose-rates near to the trabecular surfaces at 1 day were two to four times greater than corresponding results for cortical bone. Burial was most rapid for (233)U, about twice the rate in cortical bone. As in cortical bone, subsequent uptake into the marrow was seen for (239)Pu and (241)Am but not (233)U. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corresponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow.
  
  
  CONCLUSIONS
  Cumulative radiation doses to the 10 microm thick band of marrow adjacent to all endosteal surfaces were in the ratio of approximately 7:3:1 for (239)Pu:(241)Am:(233)U. This ratio is not inconsistent with observed incidences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were probably not significantly different to that for a 10 microm depth, better correlations with osteosarcomagenic risk were obtained with 20-40 microm depths. For acute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which gave a dose ratio of approximately 12:11:1 for (239)Pu:(241)Am:(233)U respectively.
authors.affiliation: CRC Experimental Haematology Group, Paterson Institute Cancer Research, Christie Hospital NHS Trust, Wilmslow Manchester M20 4BX, UK. blord@picr.man.ac.uk
authors.forename: B I
authors.initials: BI
authors.lastname: Lord
authors.forename: A L
authors.initials: AL
authors.lastname: Austin
authors.forename: M
authors.initials: M
authors.lastname: Ellender
authors.forename: J W
authors.initials: JW
authors.lastname: Haines
authors.forename: J D
authors.initials: JD
authors.lastname: Harrison
mesh_terms: D000576:Americium / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001345:Autoradiography; D001853:Bone Marrow / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005269:Femur / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; 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 / Q000493:pharmacokinetics / Q000633:toxicity*; D011874:Radiometry; D012307:Risk Factors; D014018:Tissue Distribution; D014501:Uranium / Q000493:pharmacokinetics / Q000633:toxicity*
chemical_list: D014501:Uranium; D011005:Plutonium; D000576:Americium