Interactions between estrogen, tamoxifen, octylphenol, and two polychlorinated biphenyls in murine splenocytes.
Prior exposure of cultured murine splenocytes to 17beta-estradiol (E) protects them from the membrane disrupting effects of the xenoestrogen 4-tert-octylphenol (OP). Using splenocytes isolated from male Balb/c mice, we tested whether (a) the xenoestrogen, 2', 3', 4', 5'-tetrachloro-4-biphenylol (PCB-OH), or the polychlorinated biphenyl, 3, 3', 4, 4'-tetrachlorobiphenyl (PCB 77), which displays both estrogenic and anti-estrogenic actions, would compromise the membrane integrity of the cells and (b) E or tamoxifen (TX), another ligand for the E receptor, would protect the membranes of cells exposed to the agents. We also examined possible interactions between OP, PCB-OH, and PCB 77 on the cells. Splenocytes were cultured for 24 hr. Concentrations of OP (10(-5)-10(-9) M), PCB-OH (10(-6)-10(-16) M), or PCB 77 (10(-8)-10(-12) M) significantly compromised the membrane integrity of the cultured splenocytes in a dose response manner. Concentrations of E as high as 10(-5) M or TX as high as 10(-7) M were without effect. Incubation of splenocytes in medium containing E or TX at 10(-7) M for 2 hr prior to the subsequent addition of either OP, PCB-OH or PCB 77 (final concentrations of 10(-7), 10(-7), or 10(-8) M, respectively) blocked the membrane disrupting effects. Incubation of splenocytes in medium containing 10(-7) M E starting 2 hr after the addition of OP or PCB 77 or incubation of splenocytes in medium containing 10(-7) M TX starting 2 hr after the addition of OP or PCB-OH did not block the damaging effects of OP, PCB 77, or PCB-OH on the cell membranes. No interactions were observed when various combinations of OP, PCB-OH, or PCB 77 were used. These data suggest that: (a) TX acts like E in this system, (b) a prior response of splenocytes to E or TX can protect them from the potential cytotoxic effects of OP, PCB-OH, or PCB 77; and, (c) OP, PCB-OH, and PCB 77 were not additive in their actions.
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
McCoy
G L
GL
Blake
C A
CA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010636:Phenols / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013629:Tamoxifen / Q000494:pharmacology*
C104006:2',3',4',5'-tetrachloro-4-biphenylol; D010636:Phenols; D013629:Tamoxifen; D000431:Ethanol; D004958:Estradiol; D011078:Polychlorinated Biphenyls; C105260:4-tert-octylphenol; C028451:3,4,3',4'-tetrachlorobiphenyl