polonium and Cell-Transformation--Neoplastic

Radon is by far the most important contributor to the collective dose equivalent. Most of what is known about the hazards of radon daughters comes from epidemiological studies of miners. There are a few well defined areas in which in vitro research can complement such studies: First, more data on the relative effects of differing energy (LET) alpha-particles would help: (1) understand the significance of the depth of sensitive cells in the bronchial epithelium--which varies between individuals, as well as between smokers and non-smokers, and between miners and non-miners; (2) understand the relative hazards of radon and thoron daughters. Second, reliable methods for predicting high LET responses from low LET response, would enable Japanese A-bomb survivor data to be applied with confidence. Third, understanding the effects of single-particle traversals of cells relative to multiple traversals could allow reliable extrapolation of epidemiological miner data to low exposures. Fourth, a better understanding of the nature of the interaction between tobacco and radiation damage would help predict the effect of radon on non-smokers.

Topics: Alpha Particles; Animals; Bismuth; Cell Transformation, Neoplastic; Cells; Environmental Exposure; Humans; In Vitro Techniques; Lead; Mining; Occupational Exposure; Polonium; Radon; Radon Daughters; Smoking

Rat tracheal epithelial cells exposed directly on planar 210Po sources exhibited exponential cell killing; however, no significant increase in induction of preneoplastic transformation was observed over a range of alpha-particle fluences (0.017-0.050 micron-2). In contrast, up to 10-fold increases in frequencies of preneoplastic transformants, above control levels, were observed after exposure of rat tracheal epithelial cells to similar alpha-particle fluences on 238Pu and 241Am sources. Two alternative hypotheses are evaluated as an explanation for this apparent difference in the biological effect of alpha particles emitted from different sources: (a) possible interactions between effects produced by alpha particles and by low-energy photons, which occur with 238Pu and 241Am but not with 210Po; and (b) the influence of spatial relationships between exposed cells and the surface of the planar source. The data suggest that cell-to-source spatial relationships affect both survival and transformation markedly.

Topics: Alpha Particles; Americium; Animals; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Dose-Response Relationship, Radiation; Epithelium; Linear Energy Transfer; Male; Plutonium; Polonium; Rats; Rats, Inbred F344; Trachea

Murine bone marrow contains osteogenic precursor cells that undergo differentiation during in vitro cultivation. In vitro these cells are potential target cells for alpha-irradiation-induced bone tumour formation. Under defined tissue culture conditions these differentiating cells were directly exposed to alpha-particle irradiation from the radon daughter 210Po. Po deposits in soft tissue and it was shown to be associated with marrow cells and with the extracellular marrow tissue formed in vitro. These differentiating marrow cultures showed high sensitivity to alpha-irradiation. Cell death was observed at 210Po concentrations in tissue culture medium (TCM) > 7 Bq 210Po/ml. At lower concentrations (between 1 and 5 Bq 210Po per ml TCM) proliferation was enhanced as measured by uptake of 3H-thymidine, also differentiation was stimulated as measured by alkaline phosphatase activity and incorporation of 3H-proline in newly synthesized collagen. At several times of culture, the association of 210Po with the extracellular matrix and cells was measured. These retention data enabled us to calculate the daily alpha-particle fluence. At 1 Bq 210Po present per ml tissue culture, a daily alpha-particle fluence as low as 3-6 per 1000 cells seemed very efficient in changing the expression of osteogenic differentiation of marrow cells.

Topics: 3T3 Cells; Alpha Particles; Animals; Bone Marrow; Bone Marrow Cells; Bone Neoplasms; Cell Differentiation; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Culture Media; Dose-Response Relationship, Radiation; Mice; Mice, Inbred BALB C; Neoplasms, Radiation-Induced; Osteoblasts; Osteogenesis; Polonium; Stem Cells; Stromal Cells

The oncongenic effects of radiation on rat respiratory tissues are modulated in vivo within the intact tissue. The degree of modulation as well as the mechanism whereby modulation occurs appears to be different for different types of ionizing radiations. A combined cell culture -in vivo model is described. This model has been developed to evaluate the influence of the host and tissue environment on development and expression of the neoplastic phenotype in irradiated rat trachea. Our data indicates that the potentially oncogenic effects of neutrons, X Rays, and alpha-particles are different depending on the exposure conditions employed and the conditions under which exposed cells are maintained following exposure.

Topics: Alpha Particles; Animals; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; Epithelial Cells; Epithelium; Neoplasms, Radiation-Induced; Neutrons; Polonium; Radiation Dosage; Radiation Injuries, Experimental; Rats; Trachea; Tumor Cells, Cultured; X-Rays

Rat tracheal epithelial cells exhibited exponential cell killing when exposed to 210Po alpha particles as single cell suspensions or in the intact tissue. Survival of cells in the intact tissue was not significantly different from that observed with cell suspensions. Comparison of survival of cells exposed in suspension to 300 kVpX rays yielded an RBE of 6.3. Measurements of basal cell nuclei were used to determine that a single traversal of a cell nucleus had a high probability of causing cell inactivation. This was also observed in mink lung cells and CHO cells exposed in an identical manner. There were no significant increases in frequencies of preneoplastic transformation observed for a range of exposures (0.0007 to 0.05 alpha particles/micron2). Examination of intact tracheal transplants which were irradiated with alpha particles also failed to reveal any preneoplastic or neoplastic changes.

Topics: Alpha Particles; Animals; Cell Line; Cell Survival; Cell Transformation, Neoplastic; Cells, Cultured; CHO Cells; Cricetinae; Epithelium; Male; Neoplasms, Radiation-Induced; Polonium; Precancerous Conditions; Rats; Rats, Inbred F344; Suspensions; Trachea; Tracheal Neoplasms

Topics: Animals; Cell Transformation, Neoplastic; Cricetinae; Glycoproteins; Histocytochemistry; Lung Neoplasms; Male; Mesocricetus; Microscopy, Electron; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Polonium