Effects of low doses of carcinogen and different antibodies on the splenic lymphoid system of p53 transgenic mice: morphometric and immunohistochemical studies.
The role of the splenic immune system in the development of high sensitivity of p53 transgenic mice to low doses of carcinogen and vaccination was investigated immunohistochemically and morphometrically. Spleens were obtained from human p53 promoter-chloramphenicol acetyl transferase transgenic mice, grouped as follows: 1, untreated controls; 2, exposed to dimethylhydrazine (DMH); 3, and 4, vaccinated with polyclonal antibodies to soluble-53 kDa protein (s53); 5, vaccinated with monoclonal PAb DO1; 6, vaccinated with monoclonal PAb 421; 7, vaccinated with polyclonal alphaH-p53 antibody. Mice in groups 4-7 were treated with DMH after the course of vaccination. Six months later all the mice were tumor-free, but effects of the low dose carcinogen were distinct in the splenic immune system. They were mainly manifested in blast transformation: the total number of lymphocytes and lymphoblasts decreased to 56.5% of the controls. The total of lymphoid cells in the follicles (B zone) and periarterial lymph sheath (T zone) declined, reflecting moderate insufficiency of the spleen's lymphoid system. Vaccination of transgenic mice with antibodies to soluble-p53 elicited mainly a B system response, with lesser T system involvement. Only few signs of B system insufficiency were found in these mice. Vaccination of mice with different antibodies, with subsequent carcinogen treatment, caused changes in the spleen that were similar to those described for DMH alone, but varied with different anti-p53 antibodies. Vaccination with polyclonal antibodies to soluble-p53, or with monoclonal antibodies PAb DO1 or PAb 421, stimulated the splenic activity of T system, and therefore can decrease the tumorigenic effect of carcinogens.
Laboratory of Experimental Oncology, The Koret School of Veterinary Medicine, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
P
P
Gurevich
H
H
Ben-Hur
B
B
Sandler
V
V
Berman
Y
Y
Tendler
O
O
Zinder
I
I
Zusman
D019813:1,2-Dimethylhydrazine / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000032:analysis; D002273:Carcinogens / Q000494:pharmacology*; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D002273:Carcinogens; D016159:Tumor Suppressor Protein p53; D019813:1,2-Dimethylhydrazine