Toxic effects of octylphenol on cultured rat and murine splenocytes.
Alkylphenol polyethoxylates and alkylphenols, such as 4-tertoctylphenol (OP), are environmental contaminants. Because these compounds are toxic to aquatic animals, we studied the effects of OP on splenocytes removed from male Fischer 344 rats or male Balb/c mice and cultured in vitro. Cell viability was assessed by trypan blue exclusion after 5 or 27 hr of culture. Culture with 0.08% ETOH (vehicle) or any dose of OP did not alter total cell number or the percentage of viable cells after 5 hr. Culture of cells with two different alkylphenol polyethoxylates for 5 hr resulted in the loss of all cells. The percentages of viable rat or mouse cells after 27 hr of culture were decreased significantly by 10(-12) M OP or greater concentrations. The actions of OP, dexamethasone (DEX), and 17 beta-estradiol on rat splenocytes were compared. Dexamethasone was more toxic than OP after 24 hr of culture; 17 beta-estradiol was not toxic. Dexamethasone and OP, but not 17 beta-estradiol, caused significant nuclear condensation after 3 hr of culture (acridine orange staining) or 4 hr of culture (propidium iodide staining). The toxicity of 10(-6) M OP, but not that of 10(-6) M DEX, was eliminated when mouse splenocytes were cultured in Ca2+ -free medium. Significantly more mouse splenocytes containing free 3'-OH DNA ends were detected by activated cell sorter analyses when the cells had been incubated for 4 hr with 10(-4) or 10(-6) M OP or 10(-6) M DEX. The results of these studies demonstrate that OP is toxic to cultured rat and mouse splenocytes and suggest that this toxic effect is exerted, at least partially, through Ca2+-dependent apoptosis.
Nair-Menon
J U
JU
Department of Cell Biology and Neuroscience, University of South Carolina, School of Medicine, Columbia 29208, USA.
Campbell
G T
GT
Blake
C A
CA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000633:toxicity; D004958:Estradiol / Q000633:toxicity; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010636:Phenols / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects*
D010636:Phenols; D011960:Receptors, Estrogen; D004958:Estradiol; C080417:4-octylphenol; D003907:Dexamethasone