BIOCHEMICAL AND CLINICAL EFFECTS OF SELENIUM ON DIMETHYLHYDRAZINE-INDUCED COLON CANCER IN RATS

Abstract

The biochemical and clinical effects of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Spraque-Dawley rats are presented. A 4-ppm Se supplement to the drinking water was provided before, during and after 20 weekly injections of 20 mg DMH/kg body weight. Immediately after the 20th DMH injection, some of the rats were sacrificed. The incidences of colon tumors in groups provided Se before DMH, before and during DMH, and only during DMH treatment were reduced to 39, 43 and 36%, respectively. The incidence in the DMH Only control was 63%. Other rats in all treated and control groups were maintained up to 5 mo. post-DMH treatment. At 10-wk intervals throughout the study, selected blood and tissue components were analyzed. The following hematological changes correlated with DMH treatment. Serum glutamic oxalacetic transaminase increased 2-fold (normal, 66 .+-. 14 g/dl). Serum alkaline phosphatase increased 24% (normal, 166 .+-. 56 units/l) Serum protein decreased 14% (normal, 6.77 .+-. 0.48 g/dl). White blood count increased 2- to 3-fold (normal, 7.7 .+-. 2.7 .times. 103/cu mm). Hb decreased 67% (normal, 18.1 .+-. 1.3 g/dl). The magnitude of these changes varies with each Se treatment group and with each 10-wk analysis period. Provision of 4 ppm Se doubled liver and blood Se levels compared to unsupplemented controls. The effects of Se and DMH treatments on glutathione peroxidase and .beta.-glucuronidase activities and on sialic acid are presented. Possible mechanisms by which Se protects against DMH-induced neoplasia are discussed.