The AH receptor of the most dioxin-sensitive species, guinea pig, is highly homologous to the human AH receptor

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) brings about a wide spectrum of toxic and biochemical changes, most of which are mediated by the AH recepto r (AHR). Recent cloning of the AHR from the two most TCDD-resistant laborat ory animals, Han/Wistar (Kuopio) rats and hamsters, suggested a critical ro le for the C-terminal transactivation domain structure in TCDD sensitivity. Here we cloned the AHR from the most TCDD-susceptible species, guinea pig. The N-terminus of its AHR was highly similar to that in the resistant anim als. However, the C-terminal Q-rich subdomain was only about half the size of this subunit in the hamster AHR. There was a distinct correlation across published mammalian species between the number of glutamine residues in th e Q-rich subdomain and sensitivity to the acute lethality of TCDD. The clos est homolog of the Guinea pig receptor turned out to be the human AHR, whic h may be relevant for dioxin risk assessment. (C) 2001 Academic Press.