Applicability of tyrosine hydroxylase promoter activation assay (TH assay)for screening of dioxin-like compounds
Several environmental such as polycyclic aromatic hydrocarbons (PAHs), affect human health. These chemicals also influence brain function. Thus, the development of methods for screening toxic chemicals and detecting their toxic potency is important. PAH toxicities are mainly due to the disruption of gene expression. A major participant in the process is the aryl hydrocarbon receptor (AhR) and AhR-mediated gene expression. Previously, we reported that the tyrosine hydroxylase (TH) gene was a target of AhR activated by dioxins and that a novel AhR binding element, AhRE-TH, upstream of the TH gene was identified. Since TH is a rate-limiting enzyme of dopamine synthesis, abnormal TH gene expression is thought to be correlated to the disturbance of brain function. Using the transcriptional mechanism of the TH gene, we developed a TH promoter activation assay (TH assay), which measures the activity of compounds against transcriptional regulation of the TH gene.In this study, to verify the applicability of the TH assay, we investigated the role of PAHs using this assay and calculated the 2,3,7,8-tetrachlorodibenzo-p-dioxintoxic equivalency factors (TH-TEFs). The obtained TH-TEF values corresponded to the reported WHO-TEF values. Therefore, the results demonstrate the suitability of the TH assay in assessing the toxic potency of PAHs.
Saeko Uruno Seiko Yoshimura Eiichi Akahoshi Mitsuko Ishihara-Sugano
Functional Materials Laboratory,Corporate Research & Development Center,Toshiba Corporation,1,Komukai-Toshiba-cho,Saiwai-ku,Kawasaki 212-8582,Japan
国际会议
北京
英文
1-4
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）