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Concomitant p53 Gene Mutation and Increased Radiosensitivity in Rat Lung Embryo Epithelial Cells during Neoplastic Development¹

Laboratoire de Radiobiologie Appliquée, Département de Pathologie et Toxicologie Expérimentale, CEA-Saclay, Gif sur Yvette, 91191 Cedex, France [D. S. F. B., M. M., J. L. L], and Laboratoire d'Oncologie Moléculaire, CNRS, 7 rue Guy Moquet, 94801 Villejuif Cedex, France [Y. L. R., A. D., E. M., P. M.]

A rat lung cell population had been treated with benzo(a)pyrene, and a set of different epithelial cell lines was derived from it. These cell lines carried either a wild-type or mutant p53 gene and represented grading states of neoplastic development. We demonstrate here that the cells lacking both wild-type p53 alleles display a significant decrease in survival after -irradiation with doses of 2 to 12 Gy, compared with their counterparts carrying wild-type p53 alleles. This is the first reported model in which cells bearing a mutation of the p53 gene display enhanced sensitivity to ionizing radiation.

¹ This work was supported by Grant 6986 from the Association pour la Recherche sur le Cancer and Grant F13P-CT92-0067 from the Commission of the European Community in Brussels.

² To whom requests for reprints should be addressed, at Laboratoire de Radiobiologie Appliquée, CEA-Saclay, Gif sur Yvette, 91191 Cedex, France.

Received 3/16/94. Accepted 5/23/94.

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