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 receptor (AHR). Recent cloning of the AHR from the two most TCDD-resistant laboratory animals, Han/Wistar (Kuopio) rats and hamsters, suggested a critical role 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 animals. 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 the Q-rich subdomain and sensitivity to the acute lethality of TCDD. The closest homolog of the Guinea pig receptor turned out to be the human AHR, which may be relevant for dioxin risk assessment.
Korkalainen
M
M
Laboratory of Toxicology, National Public Health Institute, Kuopio, FIN-70701, Finland. Merja.Korkalainen@ktl.fi
Tuomisto
J
J
Pohjanvirta
R
R
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004351:Drug Resistance / Q000235:genetics; D006168:Guinea Pigs; D006801:Humans; D008969:Molecular Sequence Data; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon