QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

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In vitro assays for oncogenic transformation based on rodent cells represent a powerful research tool for investigating the oncogenic potential of physical and chemical agents found in the environment because they are highly quantitative. This is particularly true of C3H 10T 1/2 cells. Three issues will be addressed, all of which relate to the primary overall goals of the program project. First, transformation incidence will be assessed for exactly 1, 2, 4 or 8 alpha-particles (LET 90 and 180 ke V/mu) compared with Poisson-distributed numbers of a-particles of the same LET and with mean traversal numbers of 1, 2, 4, or 8. This will address the question of assessing cancer risks in a domestic situation where bronchial epithelial cells are essentially never traversed by more than one particle, by extrapolation from underground miner data where multiple traversals are common. Second, experiments will be performed to investigate the effect on transformation incidence of the interaction between a-particles and arsenites which are present int he dust of underground mines. Underground miners were exposed concomitantly to all of these carcinogens. In the case of arsenates, exposure occurs only in mines and not in homes, so that all that is required is an understanding of the mode of interaction - so that allowance can be made for the arsenite effect in miners before radon risks are extrapolated to a domestic situation. By contrast, in the case of tobacco specific nitrosamines, it is also important to know if concurrent exposure to a-particles and nitrosamines influences the process of extrapolation from high to low doses of a-particles, since while essentially all miners smoked, the domestic situation includes both smokers and non-smokers. Third, the transformation incidence will be compared for a mean of five a-particles given, either to a single generation of cells, or as one particle per generation. This addresses the problem that the target cells in most underground miners, whose risks are to be extrapolated to low doses, were exposed over many cellular generations so that multiple a-particle traversals would be suffered by a cell and its progeny, rather than by a single cell. Data from all three aims will impact on the practical problem of obtaining lung cancer risk estimates for radon in homes from either the dosimetric or epidemiological approaches. They will be integrated into modelling in Project I.