The immune response of rat spleen to dietary fibers and to low doses of carcinogen: morphometric and immunohistochemical studies.
The effects of high-fiber diets on anticancer immune response are often masked by the effects of high-dose carcinogens. Using low levels of carcinogen the splenic immune response can be evaluated. Colon tumors were induced in rats with low doses of 1, 2-dimethylhydrazine, in the following experimental groups: rats fed with low fiber diet without exposure to carcinogen; rats exposed to the carcinogen and fed with low-fiber diet; rats exposed to carcinogen, and maintained on high-fiber diets, and did not develop tumors; and rats that developed tumors after exposure to carcinogen and maintenance on either low-fiber or high-fiber diets. After 24 weeks their spleens were studied immunohistochemically and morphometrically. In tumor-free rats, low doses of carcinogen caused significant response of the lymphoid system. This was manifested in the intensive blast transformation and in an increase in the number of dendritic cells and macrophages in different structures of the spleen. Dietary fibers activated these processes: the number of Ki-67 positive cells, macrophages and plasma cells increased significantly in the red pulp. A positive correlation was found between the effects of the carcinogen and proliferation of lymphocytes in the white pulp, and to lesser degree between high-fiber diets and lymphocytic abundance in the red pulp. The number of splenic apoptotic lymphocytes decreased in rats exposed to carcinogen. In tumor-bearing rats, immune insufficiency of the splenic responses was seen in the significant decrease of the areas of the mantle layer and the periarterial sheaths, as result of the decreased number of lymphocytes. Dietary fibers reduced the degree of this insufficiency. Even low doses of carcinogen cause a significant splenic immune response. This reaction has a compensatory character with macrophages, B and T cells participating. Addition of any high-fiber diet after the exposure to carcinogen activated the lymphocyte proliferation in the spleen.
Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot 76100, Israel.
I
I
Zusman
P
P
Gurevich
H
H
Benhur
V
V
Berman
B
B
Sandler
Y
Y
Tendler
Z
Z
Madar
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D004043:Dietary Fiber; D004305:Dose-Response Relationship, Drug; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
D002273:Carcinogens; D004043:Dietary Fiber; D019813:1,2-Dimethylhydrazine