TRIPHENYLSELENONIUM AND DIPHENYLSELENIDE IN CANCER CHEMOPREVENTION - COMPARATIVE-STUDIES OF ANTICARCINOGENIC EFFICACY, TISSUE SELENIUM LEVELS AND EXCRETION PROFILE

The objectives of the present study were to evaluate the cancer chemop reventive activity of triphenylselenonium chloride and diphenylselenid e and to investigate the pharmacology of these two compounds with resp ect to their tissue accumulation and excretion profile. Although both phenyl selenide derivatives are related to each other structurally, th ey differ substantially in their intrinsic chemical properties. Triphe nylselenonium is positively charged and amphiphilic, while diphenylsel enide is uncharged and lipophilic. With the use of either the DMBA-or MNU-induced mammary tumor model in rats, triphenylselenonium was found to have superior chemopreventive efficacy compared to diphenylselenid e. Both reagents were present at 30 ppm Se in the diet. At the time of sacrifice (22 weeks post-carcinogen), triphenylselenonium produced on ly minimal accumulation of selenium in the liver kidney, mammary gland and plasma. In contrast, diphenylselenide caused a 2- to 3-fold eleva tion in selenium concentration depending on the tissue examined Thus e ven though diphenylselenide was able to increase total selenium in tis sues, if was less active in cancer protection. Fecal excretion followi ng a single oral dose of triphenylselenonium (equal to the amount cons umed in 1 day by an animal fed a diet containing 30 ppm Se) was approx imately 78% and 8% of the dose during the first and second day, respec tively suggesting that the bulk of the dose was not absorbed. With dip henylselenide, fecal excretion was about 6% and 30% of the dose during the first and second day, and about 20% of the dose was excreted in t he urine in each of the 2 days. This observation suggests that a large proportion of the diphenylselenide dose was absorbed and that urinary excretion was a major route of elimination for diphenylselenide once it was absorbed. Further studies are needed to clarify the basis for t he differential effects of these phenyl selenide derivatives.