Towards molecular understanding of species differences in dioxin sensitivity: initial characterization of Ah receptor cDNAs in birds and an amphibian.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related planar halogenated aromatic hydrocarbons (PHAHs) are highly toxic to most vertebrate animals, but there are dramatic species differences in sensitivity, both within and among vertebrate classes. For example, studies in cultured avian hepatocytes have revealed differential sensitivity of birds to PHAHs [Kennedy et al. (1996). Toxicol. Appl. Pharmacol., 141, 214-230]. Differences in the characteristics or expression of the aryl hydrocarbon receptor (AHR) could contribute to these species differences in PHAH responsiveness. To investigate the molecular mechanism of differential PHAH sensitivity, we have begun to characterize the AHR in white leghorn chicken (Gallus gallus), Pekin duck (Anas platyrhynchos), and common tern (Sterna hirundo), as well as an amphibian, mudpuppy (Necturus maculosus). Partial AHR cDNAs encompassing the helix-loop-helix and PAS domains were cloned and sequenced. Comparison of amino acid sequences in this region indicated a high degree of sequence conservation among the bird species (97% amino acid identity). The percent identity between bird sequences and either mouse or mudpuppy was lower (79%); the mudpuppy AHR was 74% identical to the mouse AHR. Phylogenetic analysis of these and other AHR amino acid sequences showed that the bird and mudpuppy AHRs were more closely related to mammalian and fish AHR1 forms than to fish AHR2. Future studies include the in vitro expression and functional characterization of AHRs from these and other non-mammalian vertebrates.
Karchner
S I
SI
Biology Department, MS#32, Woods Hole Oceanographic Institution, Woods Hole, MA 02543-1049, USA.
Kennedy
S W
SW
Trudeau
S
S
Hahn
M E
ME
D000595:Amino Acid Sequence; D000818:Animals; D001717:Birds / Q000235:genetics* / Q000378:metabolism; D002645:Chickens; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D018076:DNA, Complementary / Q000737:chemistry; D004147:Dioxins / Q000633:toxicity*; D004372:Ducks; D004790:Enzyme Induction / Q000187:drug effects; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D009337:Necturus / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
D018076:DNA, Complementary; D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1