Interaction of tributyltin with 3,3',4,4',5-pentachlorobiphenyl-induced ethoxyresorufin O-deethylase activity in rat hepatoma cells.
Interaction of tributyltin (TBT) with 3,3',4,4',5-pentachlorobiphenyl (PCB-126)-induced ethoxyresorufin O-deethylase (EROD) activity was examined in vitro using H4IIE rat hepatoma cells. H4IIE cells were exposed to TBT and PCB-126, individually or in combination, at different concentrations. TBT was cytotoxic at concentrations greater than 98 nM. PCB-126 was not cytotoxic in the concentration range of 49 to 3140 pM. At concentrations greater than 49 nM, PCB-126 enhanced the cytotoxicity of TBT in the 24-98 nM range. In the absence of inducers of EROD activity, TBT significantly inhibited constitutive EROD activity in H4IIE cells in a concentration-dependent manner. EROD activity in H4IIE cells was significantly increased by exposure to PCB-126 alone. This effect was potentiated by coexposure to low, noncytotoxic concentrations of TBT. The induction of cytochrome P-4501A (CYP1A) activity in the presence of both an inducer (PCB-126) and low concentrations of an inhibitor (TBT) indicates that TBT does not interfere with the Ah receptor binding, but acts at the transcriptional level. Potentiation of EROD activity and cytotoxicity as a consequence of coexposure to PCB-126 and TBT is of considerable toxicological significance, given their coaccumulation in a variety of marine organisms.
Kannan
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National Food Safety and Toxicology Center, Department of Zoology, Michigan State University, East Lansing 48824, USA. kuruntha@pilot.msu.edu
Villeneuve
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Blankenship
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Giesy
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D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000633:toxicity; D008114:Liver Neoplasms, Experimental; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects; D014220:Trialkyltin Compounds / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D018336:Receptors, Aryl Hydrocarbon; D014220:Trialkyltin Compounds; C011559:tributyltin; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C023035:3,4,5,3',4'-pentachlorobiphenyl