Inhibition of growth by 2,3,7,8-tetrachlorodibenzo-p-dioxin in 5L rat hepatoma cells is associated with the presence of Ah receptor.
The role of the Ah receptor in mediating the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in 5L rat hepatoma cells containing TCDD-inducible cytochrome P450IA1 activity and in variants lacking cytochrome P450IA1 and Ah receptor. TCDD inhibited growth of the wild-type 5L cells, but not of the Ah receptor deficient variants. The two strong Ah receptor ligands 3,3',4,4'-tetrachlorobiphenyl (3,3',4,4'-TCB) and benz[a]anthracene (BA) exerted toxic effects in 5L cells that resembled those of TCDD. The poor Ah receptor ligand 2,2',4,4'-tetrachlorobiphenyl was not toxic in 5L cells. The concentrations of TCDD, 3,3',4,4'-TCB or BA required for the toxic response were similar to those that elicited P450IA1 induction. The present results suggest strongly that interaction with the Ah receptor is a necessary link in the chain of events leading to toxic effects in 5L cells upon exposure to TCDD.
Göttlicher
M
M
Institute of Pharmacology and Toxicology, University of Würzburg, FRG.
Cikryt
P
P
Wiebel
F J
FJ
D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004247:DNA / Q000187:drug effects; D066298:In Vitro Techniques; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000502:physiology*; D014407:Tumor Cells, Cultured
D001551:Benz(a)Anthracenes; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C035976:2,4,2',4'-tetrachlorobiphenyl; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; C030935:benz(a)anthracene; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl