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Oncogenic transformation of mouse BALB/3T3 cells by plutonium-238 alpha particles.

The A31-11 mouse BALB/3T3 cell system was adapted for the study of malignant transformation induced by 5.3 MeV alpha particles from a specially constructed 238Pu source. The biologic effects were compared to those of 220 kVp X rays. The alpha-radiation survival curve showed a D0 of 70 rad and a relative biological effectiveness (RBE) of 3.5 at 50% survival. The transformation frequency increased exponentially with dose in the range examined (25-250 rad); the maximum RBE for the induction of transformation in growing cells was approximately 3. The RBE for alpha transformation in nonproliferating cells, however, appeared to be much higher; the yield of transformants among X-irradiated cells held in the stationary phase of growth for 6 to 220 hr after irradiation declined nearly 50-fold while no decrease occurred in alpha-irradiated cells. This finding supports the hypothesis that carcinogenic damage induced by high LET radiation in mammalian cells is inefficiently repaired compared with X-ray damage, and that the carcinogenic effect of exposures to high LET radiation may be simply cumulative in nature. It further suggests that the effective RBE for alpha radiation in nonproliferating cell populations in vivo may be much higher than one would predict based on measurements in dividing cells.

Alpha Particles↗

[Characteristics of a monolayer culture of bone marrow cells in rats with plutonium 239-induced osteosarcomas].

The report is concerned with a monolayer culture of bone marrow cells of rats in which optimal blastogenic dose (92.5 kBq/kg) induced osteosarcoma. The cell culture showed an enhanced rate of fibroblast-like cell proliferation (increased number of mitoses and symplasts and larger colonies of cells), apparent signs of radiation injury (pathologic mitoses, chromosome aberrations and gaps) as well as an increase in ploidy. Diffusion chamber measurements demonstrated osteogenic precursor-cells in osteosarcoma-bearing rats to be highly capable of bone formation. This relatively high ability seems to occur outside bone marrow as well.

Animals↗

Terminal hematological changes in mice bearing osteosarcomas induced by plutonium-239.

Terminal hematological changes were studied in female ICR mice injected intravenously with 181.1 kBq/kg of monomeric 239Pu. Cellularity and differential cell counts in femoral bone marrow and spleen, as well as peripheral blood counts were determined. The results were evaluated with respect to the quantitative hematological changes and to the diagnosis of proliferative disorders. As far as the nonstochastic response is concerned, evidently decreased cell counts, without abnormalities in myelogram, were observed in the femoral bone marrow of 239Pu-treated mice and only a mild leukopenia was present in peripheral blood. No significant difference was observed between the hematological response of tumor-bearing mice and the response of mice free of osteosarcomas.

Animals↗

Primary bone neoplasms in beagle dogs exposed by inhalation to aerosols of plutonium-238 dioxide.

Primary bone neoplasms developed in beagle dogs briefly exposed by inhalation to aerosols of 238PuO2. 238PuO2 was initially deposited in the respiratory tract where it was retained with a half time greater than 100 days. A portion of the 238Pu was solubilized and translocated to the liver and skeleton. Five years after exposure, 46 osteosarcomas developed in 35 of 144 exposed dogs. The cumulative absorbed radiation doses to skeleton for these dogs ranged from 210 to 830 rad. Of the 46 bone tumors, 22 originated in the vertebrae, 12 in the humeri, 6 in the pelves, and 6 in miscellaneous long and flat bones. Most of the tumors were well-differentiated sarcomas. Only 10 of the tumors metastasized; the lung was the organ most often invaded. Bone tumors were associated with lesions of radiation osteodysplasia. The number of bone tumors found in this study indicated that inhaled 238PuO2 was an effective skeletal carcinogen. The rate of solubilization in the lung and translocation to bone may be a factor in the radiation dose pattern and type and location of bone tumors that developed after inhalation of 238PuO2.

Aerosols↗