Comparison of immune status and 1,2-dimethylhydrazine induced tumorigenesis in brown--Norway and Fischer rats. Emphasis on splenic and colonic lymphocyte function.
Sym 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis was studied in immunologically different strains of rat: the Brown--Norway which is known to be immunologically a low-responder and the Fischer a high-responder. Brown--Norway rats received a total dose of 75, 150 or 225 mg DMH/kg or vehicle and Fischer rats received 150 mg DMH/kg or vehicle over a 3-week period. Rats were killed 5 months after the final treatment. Lymphocytes were isolated from the spleen and colon from rats treated with 150 mg DMH/kg or vehicle. Natural killer (NK) cell activity and the autologous mixed lymphocyte response (AMLR) as well as colon tumor incidence were compared between the two strains. Splenic and colonic intraperithelial lymphocytes (IEL) from the Brown--Norway strain demonstrated low NK activity and reduced splenic T lymphocyte proliferation in response to autologous non-T lymphocytes. As well, colonic lamina propria lymphocyte (LPL) proliferation was low and Brown--Norway rats had a low incidence of DMH-induced colon neoplasms (7%). In comparison, the Fischer rats had more effective splenic and IEL NK killing, enhanced splenic AMLR, enhanced LPL proliferation and a higher incidence of colon tumors (20%).
D019813:1,2-Dimethylhydrazine; D000818:Animals; D003106:Colon / Q000187:drug effects / Q000276:immunology*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D004127:Dimethylhydrazines / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008297:Male; D008763:Methylhydrazines / Q000633:toxicity*; D051381:Rats / Q000276:immunology*; D011916:Rats, Inbred F344 / Q000276:immunology*; D011919:Rats, Inbred Strains / Q000276:immunology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors
D004127:Dimethylhydrazines; D008763:Methylhydrazines; D019813:1,2-Dimethylhydrazine