P53 PROTEIN EXPRESSION AND INCREASED SSCP MOBILITY SHIFTS IN THE P53 GENE IN NORMAL UROTHELIUM CULTURED FROM SMOKERS

This study provides evidence of a significantly (P = 0.018) increased level of expression of the stable conformation of p53 in normal urothe lial cells, cultured in vitro from bladder biopsies obtained from norm al smokers without malignant disease of any site, With two significant exceptions, non-smokers showed low or no expression of this protein, Past smokers appeared to segregate into high or low p53 expressers, bu t the expression was not correlated ,vith years since quitting smoking or with pack years smoked, The mean data in this group were not quite significantly different (P = 0.08) from the non-smoker group, due to the wide inter-patient variation, For most of the smoker group, pack S ears correlated with p53 expression with a mean unit of 1.7 +/- 0.37% p53 per pack year but there was a small group of very heavy smokers wh o showed lower than expected expression (similar to 0.3-0.8% p53 per p ack year), These were statistical outliers (Grubbs test), No explanati on could be found for this, Over-expression of p53 protein, often corr elates,vith mutations in the gene, but may also indicate that breakdow n of wild-type p53 has slowed, SSCP analysis of the biopsy material wa s not possible on all patients due to ethical constraints on the amoun ts of tissue which could be taken but in the cases where it was possib le the association between loss of p53 protein function and mobility s hifts in p53 exons 5-8 was confirmed with smokers having 3.5 times the number of mobility shifts detected in non-smoker DNA, Thus the result s may point to a role for the early abrogation of p53 protein function in bladder carcinogenesis induced by cigarette smoking.