ROLE OF APOPTOSIS, PROLIFERATING CELL NUCLEAR ANTIGEN AND P53 PROTEININ THE IMMUNE-RESPONSE OF RAT COLON CELLS TO CANCER AND VACCINATION WITH ANTI-P53 POLYCLONAL ANTIBODIES

Background: Previously it was shown that rabbit anti-p53 antibodies ca n exert tumor-suppressive effects on chemically induced rat colon canc er (Cancer J, 10:116-120, 1997). This work examines the role of some c omponents of the immune system in the response of the rat colon cells to treatment with a carcinogen and anti-p53 antibodies. Methods: The f ollowing groups of rats were studied: a) control non treated rats; b) tumor-free non vaccinated rats treated with a carcinogen; c) tumor-bea ring non vaccinated rats; d) tumor-free vaccinated rats exposed to a c arcinogen; e) tumor-bearing vaccinated rats. The manifestation of apop tosis, proliferating cell nuclear antigen (PCNA), mitotic index, T lym phocytes and p53 protein was compared between the different groups of rats. Results: The apoptotic index and the number of p53-positive cell s and T lymphocytes were significantly higher in colon adenocarcinomas obtained from vaccinated rats than in unvaccinated rats. PCNA was low er in tumors from the vaccinated rats, whereas the proliferating cell index was not different between the both groups of rats. An inverse re lationship was seen between apoptosis and most other parameters studie d. The inverse correlation found between apoptosis and p53 protein in this study demonstrated that apoptosis acts as a p53-independent param eter in chemically induced rat colon cancer. Conclusions: our findings demonstrated that vaccination significantly activated apoptosis in bo th types of colon tissue, and induced synthesis of p53 protein in tumo r tissue. Vaccination with anti-p53 polyclonal antibodies seemed to ac tivate the immune system and to stimulate some of its cellular compone nts responsible for tumor suppression.