EVALUATION OF BENZYL SELENOCYANATE GLUTATHIONE CONJUGATE FOR POTENTIAL CHEMOPREVENTIVE PROPERTIES IN COLON CARCINOGENESIS

Observational, clinical and experimental studies have suggested that d ietary supplementation with selenium can inhibit the development of co lon cancer. Since toxicity and chemopreventive efficacy of selenium co mpounds depend to a large extent, on the form of selenium the developm ent of efficacious organoselenium compounds with low toxicity is being pursued ih our laboratory. We have assessed the chemopreventive prope rties of a newly synthesized organoselenium compound, benzyl selenocya nate glutathione conjugate (BSeSG), and of benzyl selenocyanate (BSC), as a positive control, using azoxymethane (AOM)-induced colonic aberr ant crypt foci (ACF) as a measure of efficacy. Five-week-old male F344 rats were fed the control diet (modified AIN-76A) or experimental die ts containing 10 or 20 ppm BSeSG (1.7 and 3.4 ppm as Se, respectively) , or 10 ppm BSC (4.1 ppm as Se). One week later, all animals except th ose in vehicle (normal saline)-treated groups were s.c. injected with AOM (15 mg/kg of body weight, once weekly for 2 weeks). All animals we re sacrificed 7 weeks after the last AOM injection, and the ACF, level s of prostaglandin E-2 (PGE(2)), cyclooxygenase protein expression (CO X-1 and -2), and glutathione S-transferase type mu (GST-mu) were deter mined in the colon. As expected, dietary administration of BSC suppres sed ACF development by about 37%. In rats administered 10 or 20 ppm BS eSG, the frequencies of AOM-induced colonic ACF were significantly dec reased compared to those of rats given AOM and control diet by about 4 1% (P<0.01) and 61% (P<0.001), respectively. Administration of BSeSG i nhibited PGE(2) production (81-88% inhibition) via COX-2 synthesis in the colonic mucosa (18-60% inhibition). Also, BSeSG increased GST-mu p rotein activity in colonic mucosa (30-32% increase). These data sugges t that a newly synthesized organoselenium compound, BSeSG might be a p romising chemopreventive agent against colon carcinogenesis.