Tumor-preventive effects of the soluble p53 antigen on chemically-induced skin cancer in mice

Background. The tumor-suppressive effects of the rat soluble p53 antigen on chemically induced shin cancer in mice and the role of the spleen in the i mmune response to a carcinogen and vaccination were studied. Methods: Skin cancer was induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). Vaccination was initiated by injection of liposomes with the soluble p53 antigen (10-12 mu g/mouse) while boosters were with the p53 mixed with Freund's incomplet e adjuvant (two injections). Four months later, the spleen and tumors were removed and examined morphometrically (determination of areas bf different spleen's zones) and immunohistochemically (determination of number of B lym phocytes and macrophages, apoptotic index). The following groups of mice we re studied: A) control non treated mice; Bl) tumor-free mice treated with a carcinogen; B2) tumor-bearing mice; C1) tumor-free vaccinated mice exposed to a carcinogen; C2) tumor-bearing vaccinated mice. Results: Mice exposed to a carcinogen, which were tumor-free, displayed high proliferative activi ty of the spleenic lymphoid constitutes such as B lymphocytes and macrophag es. This was reflected in the remarkable transformation of B lymphocytes in lymphoblasts (blast transformation) and an increase in the area of germina l centers, compared to untreated controls. In tumor-bearing non vaccinated mice, significantly more spleenic apoptotic cells were found than in their tumor-free counterparts. Shrinkage of the mantle layer and a decrease in ce llular density of follicles were seen In all carcinogen-treated mice, refle cting the reduced total production of lymphoid cells, and thus the insuffic iency of the immune reaction of animals to a carcinogen. A sharp decrease i n the apoptotic index in the spleen of tumor-free mice may reflect an inhib ition of apoptotic activity of the spleen by a carcinogen. Vaccination with the soluble p53 protein decreased the incidence of tumors and their size, significantly increased the apoptotic index within tumors, and reversed the splenic parameters of immune insufficiency. Conclusions: The immune system is active during tumorigenesis. Vaccination with the soluble p53 antigen h ad positive tumor-suppressive effects. The findings may facilitate the deve lopment of vaccines for the prevention of recurrent cancers in humans.