Human cytochrome P450 CYP2A13: Predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone

T. Su, Z. Bao, Q. Y. Zhang, T. J. Smith, J. Y. Hong, X. Ding

Research output: Contribution to journalArticle

281 Citations (Scopus)

Abstract

The human CYP2A subfamily comprises three genes, CYP2A6, CYP2A7, and CYP2A13. CYP2A6 is active toward many carcinogens and is the major coumarin 7-hydroxylase and nicotine C-oxidase in the liver, whereas CYP2A7 is not functional. The function of CYP2A13 has not been characterized. In this study, a CYP2A13 cDNA was prepared by RNA-PCR from human nasal mucosa and was translated using a baculovirus expression system. In a reconstituted system, the expressed CYP2A13 was more active than CYP2A6 in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, and N-nitro-somethylphenylamine but was much less active than CYP2A6 in coumarin 7-hydroxylation. Of particular interest, CYP2A13 was highly active in the metabolic activation of a major tobacco-specific carcinogen, 4-(methylni-trosanfino)-1-(3-pyridyl)-1-buhanone, with a catalytic efficiency much greater than that of other human cytochrome P450 isoforms examined previously. The tissue distribution of CYP2A13 was determined with isoform-specific RNA-PCR. CYP2A13 mRNA was detected in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle. Quantitative PCR analysis further revealed that CYP2A13 mRNA is expressed at the highest level in the nasal mucosa, followed by the lung and the trachea. Together, these findings suggest that CYP2A13 plays important roles in xenobiotic toxicity and tobacco-related tumorigenesis in the human respiratory tract.

Original languageEnglish (US)
Pages (from-to)5074-5079
Number of pages6
JournalCancer Research
Volume60
Issue number18
StatePublished - Sep 15 2000
Externally publishedYes

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Respiratory System
Carcinogens
Cytochrome P-450 Enzyme System
Tobacco
Nasal Mucosa
Trachea
Polymerase Chain Reaction
Hempa
RNA Isoforms
Lung
Messenger RNA
Baculoviridae
Liver
Xenobiotics
Tissue Distribution
Human Mammary Glands
Hydroxylation
Thymus Gland
Small Intestine
Uterus

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Human cytochrome P450 CYP2A13 : Predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. / Su, T.; Bao, Z.; Zhang, Q. Y.; Smith, T. J.; Hong, J. Y.; Ding, X.

In: Cancer Research, Vol. 60, No. 18, 15.09.2000, p. 5074-5079.

Research output: Contribution to journalArticle

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abstract = "The human CYP2A subfamily comprises three genes, CYP2A6, CYP2A7, and CYP2A13. CYP2A6 is active toward many carcinogens and is the major coumarin 7-hydroxylase and nicotine C-oxidase in the liver, whereas CYP2A7 is not functional. The function of CYP2A13 has not been characterized. In this study, a CYP2A13 cDNA was prepared by RNA-PCR from human nasal mucosa and was translated using a baculovirus expression system. In a reconstituted system, the expressed CYP2A13 was more active than CYP2A6 in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, and N-nitro-somethylphenylamine but was much less active than CYP2A6 in coumarin 7-hydroxylation. Of particular interest, CYP2A13 was highly active in the metabolic activation of a major tobacco-specific carcinogen, 4-(methylni-trosanfino)-1-(3-pyridyl)-1-buhanone, with a catalytic efficiency much greater than that of other human cytochrome P450 isoforms examined previously. The tissue distribution of CYP2A13 was determined with isoform-specific RNA-PCR. CYP2A13 mRNA was detected in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle. Quantitative PCR analysis further revealed that CYP2A13 mRNA is expressed at the highest level in the nasal mucosa, followed by the lung and the trachea. Together, these findings suggest that CYP2A13 plays important roles in xenobiotic toxicity and tobacco-related tumorigenesis in the human respiratory tract.",
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