C. Mothersill et al., FURTHER INVESTIGATION OF THE RESPONSE OF HUMAN UROEPITHELIUM TO LOW-DOSES OF CO-60 GAMMA-RADIATION, Radiation research, 147(2), 1997, pp. 156-165
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
.