酵母を用いたほ乳動物の多環芳香族炭化水素応答系の構築
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概要
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Mutagenic and carcinogenic polyaromatic hydrocarbons (PAH) such as benzo[a]pyrene and 3-methylchoranthrene induce cellular cytochrome P450, and are metabolized by the P450. The metabolites bind to DNA bases, which lead to mutagenesis and carcinogenesis. On the other hand, some other toxic and carcinogenic hydrocarbons such as dioxins and polychlorinated biphenyls (PCB) induce the P450, but are not converted to mutagenic metabolites by the P450. The P450 induction is initiated by binding of these hydrocarbons to the cellular aryl hydrocarbon receptor (Ahr), followed by binding of the receptor to the xenobiotic responsive element that is located upstream the P450 gene. The level of activation of the Ahr pathway is roughly correlated with the toxicity of the aryl hydrocarbons. Here, we review the difference in primary structures of Ahr from vertebrates relative to their sensitivity to aryl hydrocarbons. We also describe our trial to establish recombinant yeasts for simply and rapidly measuring ligand-induced activation of Ahr from various vertebrates. Comparison in the activation of the Ahr pathway of different animals using the recombinant yeasts with the same genetic background is important for extrapolating animal data to humans.
- 日本環境変異原学会の論文
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