Further Investigation of the Response of Human Uroepithelium to Low Doses of Cobalt-60 Gamma Radiation

Abstract

Explant cultures of normal human uroepithelium were established, exposed to a range of 60Co gamma-ray doses from 0.1-5 Gy and grown for 14 days. Expression of Myc, p53 and Bc12 proteins in the epithelial cells which grew from irradiated explants was measured in situ using immunocytochemistry. The results show that overexpression of Bc12 with low Myc expression correlated with resistance to radiation as shown by the extent of growth detected on day 14. Strong staining for Myc coupled with low or absent Bc12 expression generally correlated with radiosensitivity, although the level of p53 of the culture was critical in these cases. None of the proteins on their own correlated with radiation response. What appeared to be critical was the balance of cells expressing Bc12 and Myc proteins. Building on the results presented in a previous paper which showed a division of cultures from patients into those showing monotonic and nonmonotonic responses, this study presents results for explant cultures from a greater number of patients and attempts to characterize the profile of expression of the above proteins in the uroepithelium of these patients. It shows that high Bc12/Myc ratios were found in cultures which showed a non-monotonic and resistant dose response. Where Myc was the dominant protein in the culture postirradiation, a radiosensitive and monotonic response tended to occur. Since the proteins are being detected in the distant progeny of irradiated cells, it is likely that changes induced by radiation in the cell population are stable. The measurement of these two proteins can be made in cultured biopsy material and may therefore have predictive value in radiotherapy and radiation protection. Both normal and tumor biopsies from bladder mucosa showed similar correlations between Bc12/Myc ratios and growth postirradiation.