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

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.

This publication has 0 references indexed in Scilit: