HIGH-LEVELS OF STABLE P53 PROTEIN AND THE EXPRESSION OF C-MYC IN CULTURED HUMAN EPITHELIAL TISSUE AFTER CO-60 IRRADIATION

When explants of human uroepithelium or esophageal epithelium are expo sed to acute doses of radiation (cobalt-60), the cells which grow out to form the primary cultures show a number of abnormal features. These include the development of characteristic nonsenescent. foci. These f oci have previously been shown to be c-myc positive and to have an abn ormal, tumor-like ultrastructure. Expression of c-myc and the level of stable p53 proteins have now been examined in these cultures 2 weeks after irradiation. Both proteins occurred in dividing cells at the gro wing edge of the explant and in the foci. The expression of c-myc appe ared to be correlated with growth. As expected, variation between indi vidual cultures of normal human cells was noted in the expression of s table p53 protein. Most control uroepithelial cell cultures were negat ive, but a small cohort showed a wide range of values. The control cul tures from the esophageal tissues had high expression of p53, and this decreased marginally after irradiation. Cells positive for p53 were a lways in cycle and were usually positive for c-myc as well. It would a ppear from these results that the expression of c-myc and the stable f orm of the p53 protein occur in irradiated primary cultures of normal human cells both in foci which also express a number of abnormalities and in ''edge'' cells which are dividing. Cultures of unirradiated cel ls from esophagus and a small number of uroepithelial samples had high levels of p53. Possible reasons for this are discussed.