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Drug Metabolism and Disposition Fast Forward
First published on July 13, 2005; DOI: 10.1124/dmd.105.005769

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Received for publication May 31, 2005.
Revised July 5, 2005.
Accepted for publication July 8, 2005.

EXPRESSION OF CYTOCHROME P450 AND OTHER BIOTRANSFORMATION GENES IN FETAL AND ADULT HUMAN NASAL MUCOSA

Xiuling Zhang 1, Qing-Yu Zhang 1, Dazhi Liu 1, Ting Su 1, Yan Weng 1, Guoyu Ling 1, Ying Chen 2, Jun Gu 1, Boris Schilling 3, Xinxin Ding 1*

1 Wadsworth Center, NYSDOH 2 Shandong University 3 Givaudan Fragrance Research

* Address correspondence to: E-mail: xding{at}wadsworth.org

Abstract

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-PCR and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, ALDH6, CYP1B1, CYP2F1, CYP4B1 and UGT2A1 are expressed preferentially in the nasal mucosa, and that ALDH7, FMO1, and GSTP1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.


Key words: CYP expression, extrahepatic cytochrome P450, human CYP enzymes


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