Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
OtherShort Communication

Comparative Levels of O6-Methylguanine, Pyridyloxobutyl-, and Pyridylhydroxybutyl-DNA Adducts in Lung and Liver of Rats Treated Chronically with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

Pramod Upadhyaya, Bruce R. Lindgren and Stephen S. Hecht
Drug Metabolism and Disposition June 2009, 37 (6) 1147-1151; DOI: https://doi.org/10.1124/dmd.109.027078
Pramod Upadhyaya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bruce R. Lindgren
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen S. Hecht
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung carcinogen in rats and may be a cause of lung cancer in smokers. NNK is metabolized by cytochromes P450 to intermediates that react with DNA forming methyl, pyridyloxobutyl (POB), and pyridylhydroxybutyl (PHB) adducts, which are critical in carcinogenesis. The methyl adduct O6-methylguanine (O6-methyl-G) has miscoding properties, but there are no reports on levels of this adduct in rats treated chronically with NNK in the drinking water, nor has its levels been compared with those of POB- and PHB-DNA adducts. We used liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring to quantify O6-methyl-G in lung and liver DNA of rats treated with a carcinogenic dose of 10 ppm of NNK in the drinking water and sacrificed after 1, 2, 5, 10, 16, and 20 weeks. The maximal level of O6-methyl-G in lung DNA, 2550 ± 263 fmol/mg DNA, was reached at 5 weeks and was significantly greater (P < 0.05) at that point than all other adducts (measured previously) except O2-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine. Overall levels of O6-methyl-G in lung were intermediate between those of total POB- and PHB-DNA adducts. In liver, the wave of O6-methyl-G peaked at 2 weeks while that of total POB-DNA adducts peaked at 10 weeks, and levels of total PHB-DNA adducts were low throughout. The results of this study demonstrate that substantial amounts of O6-methyl-G are formed at various time points in lung and liver DNA of rats treated chronically with NNK, supporting its role in carcinogenesis.

Footnotes

  • This work was supported in part by the National Institutes of Health National Cancer Institute [Grants CA81301, CA77598].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.109.027078.

  • ABBREVIATIONS: NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; P450, cytochrome P450; POB, pyridyloxobutyl; NNAL, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol; PHB, pyridylhydroxybutyl; O6-POB-dG, O6-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine; 7-POB-dG, 7-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxyguanosine; O2-POB-T, O2-[4-(3-pyridyl)-4-oxobut-1-yl]thymidine; O2-POB-dC, O2-[4-(3-pyridyl)-4-oxobut-1-yl]-2′-deoxycytidine; O2-POB-C, O2-[4-(3-pyridyl)-4-oxobut-1-yl]cytosine; 7-POB-G, 7-[4-(3-pyridyl)-4-oxobut-1-yl]guanine; O6-methyl-G, O6-methylguanine; O4-methyl-T, O4-methylthymidine; LC-ESI-MS/MS-SRM, liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring; MS, mass spectrometry; AGT, O6-alkylguanine-DNA-alkyltransferase.

    • Received February 6, 2009.
    • Accepted March 23, 2009.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 37 (6)
Drug Metabolism and Disposition
Vol. 37, Issue 6
1 Jun 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Comparative Levels of O6-Methylguanine, Pyridyloxobutyl-, and Pyridylhydroxybutyl-DNA Adducts in Lung and Liver of Rats Treated Chronically with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
OtherShort Communication

Comparative Levels of O6-Methylguanine, Pyridyloxobutyl-, and Pyridylhydroxybutyl-DNA Adducts in Lung and Liver of Rats Treated Chronically with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

Pramod Upadhyaya, Bruce R. Lindgren and Stephen S. Hecht
Drug Metabolism and Disposition June 1, 2009, 37 (6) 1147-1151; DOI: https://doi.org/10.1124/dmd.109.027078

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
OtherShort Communication

Comparative Levels of O6-Methylguanine, Pyridyloxobutyl-, and Pyridylhydroxybutyl-DNA Adducts in Lung and Liver of Rats Treated Chronically with the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone

Pramod Upadhyaya, Bruce R. Lindgren and Stephen S. Hecht
Drug Metabolism and Disposition June 1, 2009, 37 (6) 1147-1151; DOI: https://doi.org/10.1124/dmd.109.027078
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preincubation Effects on Inhibition of OCT1 by CsA
  • Carbamazepine Metabolite and Hypersensitivity Reactions
  • SULT4A1 Preserves Mitochondrial Function
Show more Short Communications

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics