MALIGNANT TRANSFORMATION OF HUMAN BRONCHIAL EPITHELIAL-CELLS BY RADON-SIMULATED ALPHA-PARTICLES

Epidemiological studies have shown that inhalation of radon is associated with an increased risk for bronchogenic carcinoma in uranium miners. These alpha-emitting radon daughters also represent the largest component of background radiation to the general public. In the present study, the oncogenic transforming effects of single versus multiple doses of radon-simulated alpha-particles were examined using human papillomavirus-immortalized human bronchial epithelial cells. Endpoints such as growth kinetics, resistance to serum and 12-O-tetradecanoylphorbol-13-acetate-induced terminal differentiation, anchorage-independent growth and tumorigenicity in nude mice were used to assess the various stages of transformation in the bronchial epithelial cells. We show here, for the first time, that immortalized human cells in culture can be malignantly transformed by a single 30 cGy dose of alpha-particles. Transformed cells produced progressively growing subcutaneous tumors upon inoculation into athymic nude mice. Immunofluorescent staining of keratin and isozyme analysis of the cell lines subsequently generated from these tumors indicated that the cells were of human epithelial origin. Analysis of genomic DNA from the tumorigenic cell lines using PCR amplification and restriction enzyme analysis demonstrated no point mutation at either codon 12/13 or 61 in any of the ras oncogenes examined (K-, N- and H-ras). This system provides an opportunity to study the cellular and molecular changes at the various stages in radiation carcinogenesis involving human cells.