Establishment of Reporter Yeasts for Guinea Pig and Syrian Hamster Aryl Hydrocarbon Receptor Ligand Activity

概要

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Polymorphism of the aryl hydrocarbon receptor (AhR) presumably induces genetic difference in the susceptibility of animals to aryl hydrocarbons. The activation of intracellular signaling following AhR binding to aryl hydrocarbons is highly correlated with the toxicity and carcinogenicity of these chemicals. Here we developed two reporter yeasts coexpressing AhR and AhR nuclear translocator (Arnt) proteins of a guinea pig and a Syrian hamster, known as the most sensitive and most resistant laboratory rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), respectively. We previously constructed reporter yeasts expressing human and mouse AhR/Arnt. We conducted reporter assays to measure ligand activities of TCDD, 3-methylcholanthrene, β-naphthoflavone and indirubin in these yeasts. Ligand treatment induced a dose-dependent increase in β-galactosidase activity from a reporter plasmid in all 4 yeast strains. The assays showed that yeast expressing guinea pig AhR/Arnt is most sensitive and yeast expressing Syrian hamster AhR/Arnt is most insensitive to these ligands. The yeasts expressing human and mouse AhR/Arnt were in-between. These different ligand activities reflect the species specificity of AhR/Arnt, and may be related to the susceptibility of rodents to aryl hydrocarbons.
日本環境変異原学会の論文
2006-11-30