@article{06802a372312441cab41a8b571343b71,
title = "Polycyclic aromatic hydrocarbons activate CYP3A4 gene transcription through human pregnane X receptor",
abstract = "Aryl hydrocarbon receptor (AhR) activators have been shown to induce members of the cytochrome P450 (P450) 1 family. Here we demonstrate that the AhR activators induce CYP3A4 through human pregnane X receptor (PXR). AhR activators, polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) increased CYP3A4 reporter activity and CYP3A4 mRNA expression in HepG2 cells. The CYP3A4 reporter activity was also increased by treatment with cigarette tar. The increased CYP3A4 reporter activity was clearly knocked down by the introduction of human PXR-smallinterfering RNA, but not by that of human AhR-small interfering RNA. The CYP3A4 reporter activity enhanced by overexpression of human PXR was further increased by treatment with PAHs and TCDD as well as by treatment with rifampicin. These results suggest that PAHs contained in cigarette smoke induce CYP3A4 in human liver.",
keywords = "AhR activator, CYP3A4 induction, PXR, Polycyclic aromatic hydrocarbons, TCDD",
author = "Takeshi Kumagai and Hiroyuki Suzuki and Takamitsu Sasaki and Shuhei Sakaguchi and Shinichi Miyairi and Yasushi Yamazoe and Kiyoshi Nagata",
note = "Funding Information: Received August 22, 2011; Accepted October 20, 2011 J-STAGE Advance Published Date: November 10, 2011, doi:10.2133/dmpk.DMPK-11-RG-094 *To whom correspondence should be addressed: Takeshi KUMAGAI, Ph.D., Department of Environmental Health Science, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan. Tel. +81-22-727-0134, Fax. +81-22-275-2013, E-mail: ta-kuma@ tohoku-pharm.ac.jp This work was supported in part by a Grant-in Aid for Scientific Research (C) from the Japan Society for the Promotion Science, by the High-Tech Research Center Program from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by the Program for the Promotion of Studies in Health Sciences of the Ministry of Health, Labor and Welfare of Japan.",
year = "2012",
doi = "10.2133/dmpk.DMPK-11-RG-094",
language = "English",
volume = "27",
pages = "200--206",
journal = "Drug Metabolism and Pharmacokinetics",
issn = "1347-4367",
publisher = "Japanese Society for the Study of Xenobiotics",
number = "2",
}