FURTHER INVESTIGATION OF THE RESPONSE OF HUMAN UROEPITHELIUM TO LOW-DOSES OF CO-60 GAMMA-RADIATION

Explant cultures of normal human uroepithelium were established, expos ed to a range of Co-60 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 immuno cytochemistry. The results show that overexpression of Bc12 with low M yc expression correlated with resistance to radiation as shown by the extent of growth detected on day 14. Strong staining for Myc coupled w ith low or absent Bc12 expression generally correlated with radiosensi tivity, although the level of p53 of the culture was critical in these cases. None of the proteins on their own correlated with radiation re sponse. What appeared to be critical was the balance of cells expressi ng Bc12 and Myc proteins. Building on the results presented in a previ ous paper which showed a division of cultures from patients into those showing monotonic and nonmonotonic responses, this study presents res ults for explant cultures from a greater number of patients and attemp ts to characterize the profile of expression of the above proteins in the uroepithelium of these patients. It shows that high Bc12/Myc ratio s were found in cultures which showed a non-monotonic and resistant do se response. Where Myc was the dominant protein in the culture postirr adiation, a radiosensitive and monotonic response tended to occur. Sin ce the proteins are being detected in the distant progeny of irradiate d cells, it is likely that changes induced by radiation in the cell po pulation are stable. The measurement of these two proteins can be made in cultured biopsy material and may therefore have predictive value i n radiotherapy and radiation protection. Both normal and tumor biopsie s from bladder mucosa showed similar correlations between Bc12/Myc rat ios and growth postirradiation. (C) 1997 by Radiation Research Society .