Individual variation in the expression of proteins involved in the regulation of growth and apoptosis post‐DNA damage in normal human urothelium

Abstract

AbstractThe changes in expression of five oncoproteins involved in the regulation of repair of DNA damage and postdamage proliferation of cells were measured in cultures of normal urothelium from over 60 patients. The results for oncoprotein expression were correlated with apoptotic index and growth rate postexposure. Both radiation and a metabolite of nitrosamine found in urine led to increased levels of p53 in cultured urothelium. There was significant interpatient variation. PCR‐SSCPE (single strand conformational polymorphism electrophoresis) analysis of foci occurring in the exposed cultures showed multiple mobility shifts in exons 5–8 of the p53 gene. These were present in irradiated cultures at high frequency, but they were only present in two of six cultures exposed to nitrosamine. Cells surrounding foci, although they were p53+ by immunocytochemistry, were mainly negative for mutations using SSCPE analysis. Expression of bcl‐2 was significantly increased following radiation exposure, but it was unchanged following nitrosamine treatment. EGFr and p21ras were uniformly increased in all carcinogen‐exposed cultures The results suggest that an early breakdown in control mechanisms of growth arrest and apoptosis may occur in urothelium following carcinogen exposure. The problem of interindividual variation in response must be considered in studies of this sort. © 1995 Wiley‐Liss, Inc.