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|RADON EXPOSURE AND CARCINOGENIC CELL TRANSFORMATION The highest radiation burden to miners is due to inhalation of radon and its short-lived decay products. The quantification of the risk associated with this radiation burden is complicated by modeldependent lung dosimetry, insufficient accuracy of past human exposure data as well as lacking knowledge about potential synergism of various carcinogens. Nevertheless, it is evident from epidemiological studies of miners that inhalation of elevated levels of radon daughters is correlated with increased lung cancer incidence (UNSCEAR, 1977). The situation is further complicated by the lack of reliable data on the biological variability of the latency period for the development of lung tumor under varying exposure conditions. At present information on variation with age is scarce, however, it is indicated that the excess lung cancer rate for workers exposed to high radon levels is considerably higher, if exposure occurs at ages over 40 years as compared to under 30 years of age (Sevc, Kunz, Placek, 1976). Furthermore, latency period is shorter by 6 - 7 years for smokers exposed to elevated radon levels than for non-smokers (Fry, 1976). Analysis of US- and CSR-uranium miner data revealed that the mean latency period is in the order of about 15 years (Jacobi, 1973). These uncertainties, together with medical diagnostic shortcomings, lead to the dissatisfying situation that at present the detection of radon induced injury of mining personal is primarily the assessment of the endpoint, i.e. radiation induced cancerous transformation of lung cells with typically less than 10% chance for recovery. Therefore it would be advantageous to develop practically applicable diagnostic aids to indicate already early precancerogenic changes of cell characteristics. This would permit the identification of specific population groups at increased risk for the development of lung cancer, thereby increasing the chances of more successful medical treatment. Despite continuous improvements in the reliability of test methods for the diagnosis of cancer cells there is still need for techniques, which enable the detection of transformed cells before the onset of invasion of the host organism. It is generally recognized that the transformation of a cell into a malignant state leads to a change of the cell surface, indicating a correlation between membrane-specific immunological properties and loss of growth control. Surface alterations on cells appear to be responsible in part for the malignant state and are not simply secondary effects of the transformation (Schnebli and Burger, 1973). Furthermore, membranes of cancer cells differ significantly from those of normal cells, particularly, in permeability properties (Rastogi, 1976). In dying cells, proteins, glycoproteins, peptides, aminoacids and their breakdown products are released, which block the permeation of the membrane itself. A mammalian cell can be considered as a 3-phase system (interior, boundary, environment) with the membrane forming a heterogeneous barrier between two subsystems. Under normal circumstances a difference of chemical potential is maintained on both sides of the membrane, causing an ion gradient across and fixed surface charges on the membrane. This results in a membrane resting potential (MRP) between cytoplasm and the bulk medium. It has been shown that MRP is a highly sensitive indicator for cellular reactions due to physical, chemical and biological agents, particularly whenever phenomena of transport and ion gradients as well as permeability are involved (Redmann, 1980). The primary interaction of the agent "ionizing radiation" with any form of living matter occurs at the cellular level. The component with the highest hit probability is the cell membrane. In the study presented MRP-changes of human cells were investigated with simultaneous measurements during irradiation and post-irradiation intervals up to six days. Furthermore, the suitability of MRP-measurements of human cells was tested as an indicator for early changes of cellular properties prior to the histological confirmation of carcinogenic transformation. EXPERIMENTAL METHODS Lung cells The biological specimen used were cultured human lung cells and human lung biopsy samples. Monolayers of lung fibroblasts (W138) were grown in petridishes using conventional culture techniques. In addition, transformed lung cells (W138SV13, subline 2RA) were used applying similar culture methods. All petridishes were incubated at 37°C and only cells in logarithmic growth phase were used. Freshly excised lung biopsy samples were obtained from randomly selected male and female patients (20 cases), where suspected or unclear malignancies were indicated by clinical or X-ray observations. At the time of sampling 80 % of the patients were or had been smokers in the past. The samples were taken by means of a stiff bronchoscope introduced into the trachea under local anasthesia with 1 % Novesinsolution (preparation with Atropin and Pantopen). This permitted the observation of both main bronchi down to the segmental bronchials. From each patient two tissue samples were excised from the mucusepithelial layer under visual control with fiber optics and transferred immediately into 1 % NaClsolution. One sample was taken from the suspected|