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Drug Metabolism and Disposition Fast Forward
First published on June 30, 2006; DOI: 10.1124/dmd.106.011049

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Received for publication May 12, 2006.
Revised June 23, 2006.
Accepted for publication June 27, 2006.

CYP2A13 in Human Respiratory Tissues and Lung Cancers: An Immunohistochemical Study with A New Peptide-specific Antibody

Liang-Ru Zhu 1, Paul E. Thomas 2, Gang Lu 2, Kenneth R. Reuhl 2, Guang-Yu Yang 3, Li-Dong Wang 4, Shou-Lin Wang 5, Chung S. Yang 2, Xiao-Yang He 5, Jun-Yan Hong 5*

1 School of Public Health,UMDNJ; Union Hospital, Huazhong Science & Technology University, Wuhan,China 2 Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey 3 Northwestern University, Chicago 4 Zhengzhou University, Zhengzhou, China 5 School of Public Health, University of Medicine and Dentistry of New Jersey

* Address correspondence to: E-mail: jyhong{at}eohsi.rutgers.edu

Abstract

Human Cytochrome P450 2A13 (CYP2A13) is highly efficient in the metabolic activation of a tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and another potent carcinogen aflatoxin B1 (AFB1). Although previous studies demonstrated that CYP2A13 mRNA is predominantly expressed in human respiratory tissues, expression of CYP2A13 protein in these tissues and the involved cell types have not been determined due to the lack of CYP2A13-specific antibodies. To explore the toxicological and physiological function of CYP2A13, it is important to understand the tissue/cellular distribution of CYP2A13 protein. In this study, we generated a peptide-specific antibody against human CYP2A13 and demonstrated by immunoblot analysis that this antibody does not cross-react with heterologously expressed human CYP2A6 and mouse CYP2A5 proteins, both sharing a high degree of amino acid sequence similarity with CYP2A13. Nor does the antibody cross-react with heterologously expressed human CYP3A4, CYP2S1 or any of the CYP enzymes present in the human liver microsomes. Using this highly specific antibody for immunohistochemical staining, we detected a high level of CYP2A13 protein expression in the epithelial cells of human bronchus and trachea, but a rare distribution in the alveolar cells. There was little expression of CYP2A13 protein in different types of lung cancers. In consideration of the high efficiency of CYP2A13 in NNK metabolic activation, our result is consistent with the reported observations that most smoking-related human lung cancers are bronchogenic and supports that CYP2A13-catalyzed in situ activation may play a critical role in human lung carcinogenesis related to NNK and AFB1 exposure.


Key words: antibodies, antigenicity, CYP expression, CYP2A, extrahepatic cytochrome P450, human CYP enzymes, lung cancer, lung cytochrome P450


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