CELLULAR AND METABOLIC EFFECTS OF TRIPHENYLSELENONIUM CHLORIDE IN A MAMMARY CELL-CULTURE MODEL

Triphenylselenonium chloride, a novel synthetic organic selenium compo und in which selenium is bonded to three unsubstituted benzene rings, possesses significant chemopreventive activity against chemically-indu ced mammary carcinogenesis. The effects of triphenylselenonium chlorid e on a mammary tumor cell line (MOD) were compared to selenite, a refe rence compound in selenium chemoprevention research. It was observed t hat triphenylselenonium chloride treatment exerted a cytostatic effect in the absence of membrane damage or DNA strand breaks. The observed cytostasis was associated with a selenium concentration-dependent inhi bition of cell proliferation, measured by [H-3]thymidine incorporation into DNA, and delayed cell cycle progression. In contrast, selenite t reatment rapidly induced DNA damage and cell death. These marked diffe rences were observed across the same levels of cellular selenium. In a ddition, triphenylselenonium chloride treatment ment increased glucose consumption and lactate production, indicating an effect of the compo und on cellular energy metabolism, Collectively these observations dem onstrate that the toxic activities associated with selenite treatment do not occur when cells are treated with triphenylselenonium chloride, This compound represents a new type of selenium compound that exerts significant cellular effects through mechanisms distinct from those in duced by selenite.