Tumorigenic target cell regions in bone marrow studied by localized dosimetry of Pu-239, Am-241 and U-233 in the mouse femur

Purpose : To study the temporal change in microdistribution of plutonium-23 9, americium-241 and uranium-233 in the mouse distal femur and to compare a nd combine calculated radiation doses with those obtained previously for th e femoral shaft. Also, to relate doses to relative risks of osteosarcoma an d acute myeloid leukaemia. Materials and methods : Computer-based image analysis of neutron-induced an d alpha -track autoradiographs of sections of mouse femora was used to quan tify the microdistribution of Pu-239, Am-241 and U-233 from 1 to 448 days a fter intraperitoneal injection. Localized dose-rates and cumulative doses o ver this period were calculated for different regions of the marrow spaces in trabecular bone. The results were then combined with previous data for d oses to the cortical marrow of the femoral shaft. A morphometric analysis o f the distal femur was carried out. Results: Initial deposition on endosteal surfaces and dose-rates near to th e trabecular surfaces at 1 day were two to four times greater than correspo nding results for cortical bone. Burial was most rapid for U-233, about twi ce the rate in cortical bone. As in cortical bone, subsequent uptake into t he marrow was seen for Pu-239 and Am-241 but not U-233. Cumulative doses to 448 days for different regions of trabecular marrow were greater than corr esponding values for cortical marrow for each radionuclide. Combined doses reflected the greater overall volume of cortical marrow. Conclusions : Cumulative radiation doses to the 10 mum thick band of marrow adjacent to all endosteal surfaces were in the ratio of similar to7:3:1 fo r Pu-239: Am-241: U-233. This ratio is not inconsistent with observed incid ences of osteosarcoma induction by the three nuclides. Analysis of doses to different depths of marrow, however, showed that although ratios were prob ably not significantly different to that for a 10 mum depth, better correla tions with osteosarcomagenic risk were obtained with 20-40 mm depths. For a cute myeloid leukaemia, the closest relationship between relative risk and doses was obtained by considering only the central 5-10% of marrow, which g ave a dose ratio of similar to 12:11:1 for Pu-239: Am-241: U-233 respective ly.