Effects of low doses of carcinogen and different antibodies on the spleniclymphoid system of p53 transgenic mice: Morphometric and immunohistochemical studies

The role of the splenic immune system in the development of high sensitivit y of p53 transgenic mice to low doses of carcinogen and vaccination was inv estigated immunohistochemically and morphometrically, Spleens were obtained from human p53 promoter-chloramphenicol acetyl transferase transgenic mice , grouped as follows: 1, untreated controls; 2, exposed to dimethylhydrazin e (DMH); 3, and 4, vaccinated with polyclonal antibodies to soluble-53 kDa protein (s53); 5, vaccinated with monoclonal PAb DO1; 6, vaccinated with mo noclonal PAb 421; 7, vaccinated with polyclonal alpha H-p53 antibody. Mice in groups 4-7 were treated with DMH after the course of vaccination. Six mo nths later all the mice were tumor-free, but effects of the low dose carcin ogen were distinct in the splenic immune system. They were mainly manifeste d in blast transformation: the total number of lymphocytes and lymphoblasts decreased to 56.5% of the controls. The total of lymphoid cells in the fol licles (B zone) and periarterial lymph sheath (T zone) declined, reflecting moderate insufficiency of the spleen's lymphoid system. Vaccination of tra nsgenic mice with antibodies to soluble-p53 elicited mainly a B system resp onse, with lesser T system involvement. Only few signs of B system insuffic iency were found in these mice. Vaccination of mice with different antibodi es, with subsequent carcinogen treatment, caused changes in the spleen that were similar to those described for DMH alone, but varied with different a nti-p53 antibodies. Vaccination with polyclonal antibodies to soluble-p53, or with monoclonal antibodies PAb DO1 or PAb 421, stimulated the splenic ac tivity of T system, and therefore can decrease the tumorigenic effect of ca rcinogens.