Selenium inhibition of 1,2-dimethylhydrazine-induced colon carcinogenesis.
The inhibitory effect of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats is presented. A 4-ppm selenium supplement to the drinking water was provided concurrently with DMH treatment and continued until death or sacrifice. Rats were administered 10 weekly injections of 10 mg DMH per kg body weight. Thirtyone weeks following the tenth DMH injection, all surviving animals were sacrificed. At sacrifice, the colon tumor incidence in DMH-only controls was 8 of 28 (29%). Selenium supplementation significantly (p less than 0.01) reduced the colon tumor incidence to 1 of 37 (3%). The cumulative colon tumor incidence for all animals found dead or sacrificed was also significantly (p less than 0.05) reduced from 11 of 40 in DMH controls to 3 of 40 in DMH-selenium-supplemented rats. The total number of colon tumors was reduced from 13 to 3, and the average number of tumors per rat from 1.2 to 1.0 by supplemental selenium. The majority (greater than 65%) of all tumors were located in the distal colon. The serum glutamic oxaloacetic transaminase, alkaline phosphatase, and complete blood count were normal and equivalent for the DMH only, DMH-selenium, and untreated control groups in this study. The glutathione S-transferase activity in liver cytosol preparations was increased from 39.6 +/- 7.3 (S.D.) microM product/min/mg (DMH only) to 67.6 +/- 5.8 microM product/min/mg by selenium only and to 54.3 +/- 10.6 microM product/min/mg in selenium-DMH-treated rats. Protection by selenium may in part be attributed to enhanced detoxification of carcinogenic electrophiles.
D019813:1,2-Dimethylhydrazine; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines / Q000633:toxicity*; D004906:Erythrocyte Count; D006400:Hematocrit; D007958:Leukocyte Count; D008297:Male; D008763:Methylhydrazines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*
D002273:Carcinogens; D004127:Dimethylhydrazines; D008763:Methylhydrazines; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase; D012643:Selenium; D019813:1,2-Dimethylhydrazine