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ToxSci Advance Access originally published online on March 7, 2003
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Toxicological Sciences 72, 253-259 (2003)
Copyright © 2003 by the Society of Toxicology

ENVIRONMENTAL TOXICOLOGY

Expression of Aryl Hydrocarbon Receptor Repressor in Normal Human Tissues and Inducibility by Polycyclic Aromatic Hydrocarbons in Human Tumor-Derived Cell Lines

Yuki Tsuchiya, Miki Nakajima, Satsuki Itoh, Masashi Iwanari and Tsuyoshi Yokoi1

Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa 920-0934, Japan

Aryl hydrocarbon receptor repressor (AhRR) has been recently identified as a negative factor that suppresses aryl hydrocarbon receptor (AhR)-mediated transcriptional gene expression. In the present study, the expression level of AhRR in normal human tissues was determined. AhRR mRNA was detected in liver, breast, colon, kidney, lung, bladder, uterus, testis, ovary, and adrenal gland. The expression level in the testis was prominently high. AhRR mRNA was also detected in various human tissue–derived cell lines, HepG2 (hepatocellular carcinoma), MCF-7 (breast carcinoma), LS-180 (colon carcinoma), ACHN (renal carcinoma), A549 (lung carcinoma), HT-1197 (bladder carcinoma), HeLa (cervix of uterus adenocarcinoma), NEC14 (testis embryonal carcinoma), and OMC-3 (ovarian carcinoma). Since the expression level of AhRR mRNA was prominently high in HeLa cells, it is suggested that the high expression level of AhRR might work as a negative factor for the low inducibility of the CYP1 family in HeLa cells. The expression of AhRR mRNA was induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3-methylchoranthrene (3-MC) in HepG2, MCF-7, LS-180, and OMC-3 cells, but not in ACHN, A549, HT-1197, HeLa, and NEC14 cells. The responsiveness was similar to the cell-specific inducibility of the CYP1 family. The inducibility of AhRR mRNA by nitropolycyclic aromatic hydrocarbons (NPAHs) as well as their parent PAHs was compared in HepG2 and OMC-3 cells. The chemical-specific inducibility of AhRR was also similar to that of the CYP1 family determined in our previous study. These results indicated that AhRR is also induced in chemical- and cell-specific manners.

Key Words: aryl hydrocarbon receptor repressor; aryl hydrocarbon receptor; aryl hydrocarbon receptor nuclear translocator; cytochrome P450; induction; TCDD.


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