Inhibiton of growth by 2,3,7,8-terachlorodibezo-p-dioxin in 5l rat hepatoma cells is associated with the presence of ah receptor

Martin Göttlicher, Peter Cikryt, Friedrich J. Wiebel

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37 Scopus citations

Abstract

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 P4SOIA1 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 [α]anthracene (BA) exerted toxic effects in 5L cells that resembled those of TCDD. The poor Ah receptor ligand 2,2' ,4,4'-tetrachloroblphenyl 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 interac tion with the Ah receptor is a necessary link in the chain of events leading to toxic effects in 5L cells upon exposure to TCDD.

Original languageEnglish
Pages (from-to)2205-2210
Number of pages6
JournalCarcinogenesis
Volume11
Issue number12
DOIs
StatePublished - Dec 1990
Externally publishedYes

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