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Expression of cytochrome P450 2A3 in rat esophagus: relevance to N-nitrosobenzylmethylamine

Expression of cytochrome P450 2A3 in rat esophagus: relevance to N-nitrosobenzylmethylamine N- nitrosobenzylmethylamine (NBzMA) must be metabolically activated to exert its carcinogenic potential and is a potent inducer of tumors in the rat esophagus. The activation is believed to occur in the esophagus. Although the pathways of NBzMA metabolism are well studied, the principal cytochrome P450 enzyme(s) (P450) responsible for catalyzing its activation is unknown. Several preliminary studies have suggested that this enzyme may belong to the P450 2A family. We report here that P450 2A3 expressed in a baculovirus system metabolizes NBzMA, predominantly by methylene hydroxylation. To determine whether or not P450 2A3 is present in the rat esophagus, the relative level of P450 2A3 mRNA was determined by reverse transcriptase–polymerase chain reaction (RT–PCR). The mRNA levels of P450 2A3 were compared with the levels of P450 2A1 and 2A2 mRNA in the esophagus, liver, lung and nasal mucosa. P450 2A3 mRNA was detected in rat nasal mucosa, lung and esophagus, but not in liver, whereas P450 2A1 and 2A2 mRNAs were detected only in the liver. To determine the relative expression of P450 2A3 in each tissue, quantitative RT–PCR with PCR-MIMICS used as internal standards was performed. The expression level in the nasal mucosa was by far the greatest. The expression in the lung and esophagus was 60- and 1600-fold less, respectively. Using antibodies to P450 2A4/5 and P450 2A10/11 a 50 kDa immunoreactive protein was detected in all three tissues by western blot analysis. This is consistent with the expression of P450 2A3 in these tissues. However, the amount of protein detected in the nasal mucosa was much greater than that in the esophagus or lung. The expression of P450 2A protein was similar in the lung and esophagus. The rate of coumarin 7-hydroxylation in cultured rat esophagus was very low. This is a reaction efficiently catalyzed by P450 2A5, 2A6 and 2A10. In summary, our results clearly demonstrate the presence of P450 2A3 protein and mRNA in the esophagus, but the amounts are low and may not be sufficient to account for NBzMA activation in this tissue. © Oxford University Press « Previous | Next Article » Table of Contents This Article Carcinogenesis (1999) 20 (5): 885-891. doi: 10.1093/carcin/20.5.885 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Carcinogenesis Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Gopalakrishnan, R. Articles by Murphy, S. E. Search for related content PubMed PubMed citation Articles by Gopalakrishnan, R. Articles by Morse, M. A. Articles by Lu, J. Articles by Weghorst, C. M. Articles by Sabourin, C. L. Articles by Stoner, G. D. Articles by Murphy, S. E. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue October 2015 36 (10) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 5.334 5-Yr impact factor: 5.698 Editor-in-Chief Dr Curtis C Harris, USA View full editorial board For Authors Instructions to authors Online submission Submit Now! Self archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("MED00710"); Most Most Read Apoptosis in cancer Modulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead Tumor progression and metastasis Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability » View all Most Read articles Most Cited Oxyradicals and DNA damage Sensing and repairing DNA double-strand breaks Functional role of estrogen metabolism in target cells: review and perspectives Apoptosis in cancer Nucleotide excision repair and human syndromes » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. 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Expression of cytochrome P450 2A3 in rat esophagus: relevance to N-nitrosobenzylmethylamine

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Publisher
Oxford University Press
Copyright
Copyright © 2015 Oxford University Press
ISSN
0143-3334
eISSN
1460-2180
DOI
10.1093/carcin/20.5.885
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Abstract

N- nitrosobenzylmethylamine (NBzMA) must be metabolically activated to exert its carcinogenic potential and is a potent inducer of tumors in the rat esophagus. The activation is believed to occur in the esophagus. Although the pathways of NBzMA metabolism are well studied, the principal cytochrome P450 enzyme(s) (P450) responsible for catalyzing its activation is unknown. Several preliminary studies have suggested that this enzyme may belong to the P450 2A family. We report here that P450 2A3 expressed in a baculovirus system metabolizes NBzMA, predominantly by methylene hydroxylation. To determine whether or not P450 2A3 is present in the rat esophagus, the relative level of P450 2A3 mRNA was determined by reverse transcriptase–polymerase chain reaction (RT–PCR). The mRNA levels of P450 2A3 were compared with the levels of P450 2A1 and 2A2 mRNA in the esophagus, liver, lung and nasal mucosa. P450 2A3 mRNA was detected in rat nasal mucosa, lung and esophagus, but not in liver, whereas P450 2A1 and 2A2 mRNAs were detected only in the liver. To determine the relative expression of P450 2A3 in each tissue, quantitative RT–PCR with PCR-MIMICS used as internal standards was performed. The expression level in the nasal mucosa was by far the greatest. The expression in the lung and esophagus was 60- and 1600-fold less, respectively. Using antibodies to P450 2A4/5 and P450 2A10/11 a 50 kDa immunoreactive protein was detected in all three tissues by western blot analysis. This is consistent with the expression of P450 2A3 in these tissues. However, the amount of protein detected in the nasal mucosa was much greater than that in the esophagus or lung. The expression of P450 2A protein was similar in the lung and esophagus. The rate of coumarin 7-hydroxylation in cultured rat esophagus was very low. This is a reaction efficiently catalyzed by P450 2A5, 2A6 and 2A10. In summary, our results clearly demonstrate the presence of P450 2A3 protein and mRNA in the esophagus, but the amounts are low and may not be sufficient to account for NBzMA activation in this tissue. © Oxford University Press « Previous | Next Article » Table of Contents This Article Carcinogenesis (1999) 20 (5): 885-891. doi: 10.1093/carcin/20.5.885 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free Classifications Carcinogenesis Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Gopalakrishnan, R. Articles by Murphy, S. E. Search for related content PubMed PubMed citation Articles by Gopalakrishnan, R. Articles by Morse, M. A. Articles by Lu, J. Articles by Weghorst, C. M. Articles by Sabourin, C. L. Articles by Stoner, G. D. Articles by Murphy, S. E. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue October 2015 36 (10) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 5.334 5-Yr impact factor: 5.698 Editor-in-Chief Dr Curtis C Harris, USA View full editorial board For Authors Instructions to authors Online submission Submit Now! Self archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("MED00710"); Most Most Read Apoptosis in cancer Modulation of E-cadherin expression by K-Ras; involvement of DNA methyltransferase-3b Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead Tumor progression and metastasis Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability » View all Most Read articles Most Cited Oxyradicals and DNA damage Sensing and repairing DNA double-strand breaks Functional role of estrogen metabolism in target cells: review and perspectives Apoptosis in cancer Nucleotide excision repair and human syndromes » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1460-2180 - Print ISSN 0143-3334 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); try { var pageTracker = _gat._getTracker("UA-189672-16"); pageTracker._setDomainName(".oxfordjournals.org"); pageTracker._trackPageview(); } catch(err) {}

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Carcinogenesis – Oxford University Press

Published: May 1, 1999

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