ESTROGEN CAN PROTECT SPLENOCYTES FROM THE TOXIC EFFECTS OF THE ENVIRONMENTAL-POLLUTANT 4-TERT-OCTYLPHENOL

Four-tert-octylphenol (OF), an environmental pollutant, exerts apoptot ic effects on cultured mouse splenocytes, Although OP binds to estroge n receptors, these apoptotic effects are not exerted by 17 beta-estrad iol (E), It remained possible that OP might bind to estrogen receptors and subsequently exert apoptotic effects not exerted by E after it bi nds to the same receptors. It also remained possible that E-primed spl enocytes might respond to OP differently than splenocytes not exposed to E, Thus, we investigated OP and E interactions on the viability of mouse splenocytes in culture. The total number of splenocytes (cells s tained and not stained with trypan blue) was not altered or altered sl ightly after incubation with any agent for 24 h, Incubation of splenoc ytes in medium containing 5 x 10(-5) or 5 x 10(-7)M OP decreased the p ercentage of viable cells by approx 47% and 25%, respectively, The add ition of 0.8 x 10(-5) to 0.8 x 10(-9)M E to cultures was without effec t or decreased the percentage of viable cells by only approx 5%. The a ddition of these concentrations of E simultaneously with or at 2 h aft er the addition of 5 x 10(-5)M or 5 x 10(-7)M OP to cultures did not i nterfere with the OF-induced decreases in cell viability, By contrast, incubation of splenocytes in medium containing E for 2 h prior to the subsequent addition of either dose of OP blocked the OF-induced decre ases in cell viability in a dose-response manner. There was a marked r eduction in the percentage of viable cells (70%) when splenocytes were incubated with 0.5 x 10(-5)M dexamethasone. The addition of 0.8 x 10( -5)M E at 2 h prior to the addition of dexamethasone did not prevent t he decreased cell viability, Incubation of cells in medium with 0.8 x 10(-5)M testosterone caused a small decrease in splenocyte viability s imilar to that observed with E, However, unlike E, the addition of tes tosterone at 2 h prior to the addition of 5 x 10(-5)M OP did not preve nt the OF-induced decrease in cell viability, These data suggest the p resence of estrogen receptors in some splenocytes. They also suggest t hat if OP binds to these estrogen receptors or other receptors in the absence or initial presence of E, the resulting effect is toxic to the cells. By contrast, exposure of splenocytes to E prior to their expos ure to OP can prevent the toxicity of OF.