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
Research ArticleArticle

QUANTITATIVE DETERMINATION OF ARISTOLOCHIC ACID-DERIVED DNA ADDUCTS IN RATS USING 32P-POSTLABELING/POLYACRYLAMIDE GEL ELECTROPHORESIS ANALYSIS

Huan Dong, Naomi Suzuki, Maria C. Torres, Radha R. Bonala, Francis Johnson, Arthur P. Grollman and Shinya Shibutani
Drug Metabolism and Disposition July 2006, 34 (7) 1122-1127; DOI: https://doi.org/10.1124/dmd.105.008706
Huan Dong
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naomi Suzuki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria C. Torres
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Radha R. Bonala
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francis Johnson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arthur P. Grollman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinya Shibutani
  • 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

Aristolochic acids (AA) are nephrotoxic and carcinogenic nitroaromatic compounds produced by the Aristolochiaceae family of plants. Ingestion of these phytotoxins by humans results in a syndrome known as AA nephropathy, characterized by renal tubulointerstitial fibrosis and upper urothelial cancer. After activation by cellular enzymes, AA I and II react with DNA to form covalent adducts and as such represent potential biomarkers for studies of AA toxicity. Using site-specifically modified oligodeoxynucleotides as standards, we have developed a method for quantifying 7-(deoxyadenosin-N6-yl) aristolactam-DNA or 7-(deoxyguanosin-N2-yl) aristolactam-DNA adducts in tissues of Wistar rats using an assay in which 32P-postlabeling techniques are coupled with nondenaturing polyacrylamide gel electrophoresis. The limit of detection with this technique is five adducts in 109 nucleotides for a 5-μg DNA sample. In contrast to previous reports, we find that the levels of AA adducts in renal tissues of Wistar rats treated p.o. with AA for 1 week with 5 mg/kg/day of AA I or AA II were much higher than that in the forestomach. Highest adduct levels were observed in rats treated with AA II, suggesting that this compound may be more genotoxic than AA I. Treatment of rats with aristolactam I, an end-product of AA I metabolism, resulted in a much lower level of adduction. This study establishes the feasibility of using AA-DNA adducts as intermediate biomarkers of exposure in studies of AA nephropathy and its associated urothelial cancer.

Footnotes

  • This research was supported by a Catacosinos Cancer Scholar Award from the School of Medicine, SUNY Stony Brook and Grant ES04068 from the National Institutes of Environmental Health Sciences.

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

  • doi:10.1124/dmd.105.008706.

  • ABBREVIATIONS: AA, aristolochic acid(s); AA I, aristolochic acid I; AA II, aristolochic acid II; L I, aristolactam I; dA-AA I, 7-(deoxyadenosin-N6-yl) aristolactam I; dG-AA I, 7-(deoxyguanosin-N2-yl) aristolactam I; dA-AA II, 7-(deoxyadenosin-N6-yl) aristolactam II; PAGE, polyacrylamide gel electrophoresis; HPLC, high-performance liquid chromatography; MALDI-TOF, matrix-assisted laser desorption ionization-time of flight.

    • Received November 30, 2005.
    • Accepted April 5, 2006.
  • 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: 34 (7)
Drug Metabolism and Disposition
Vol. 34, Issue 7
1 Jul 2006
  • 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.
QUANTITATIVE DETERMINATION OF ARISTOLOCHIC ACID-DERIVED DNA ADDUCTS IN RATS USING 32P-POSTLABELING/POLYACRYLAMIDE GEL ELECTROPHORESIS ANALYSIS
(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
Research ArticleArticle

QUANTITATIVE DETERMINATION OF ARISTOLOCHIC ACID-DERIVED DNA ADDUCTS IN RATS USING 32P-POSTLABELING/POLYACRYLAMIDE GEL ELECTROPHORESIS ANALYSIS

Huan Dong, Naomi Suzuki, Maria C. Torres, Radha R. Bonala, Francis Johnson, Arthur P. Grollman and Shinya Shibutani
Drug Metabolism and Disposition July 1, 2006, 34 (7) 1122-1127; DOI: https://doi.org/10.1124/dmd.105.008706

Citation Manager Formats

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

Share
Research ArticleArticle

QUANTITATIVE DETERMINATION OF ARISTOLOCHIC ACID-DERIVED DNA ADDUCTS IN RATS USING 32P-POSTLABELING/POLYACRYLAMIDE GEL ELECTROPHORESIS ANALYSIS

Huan Dong, Naomi Suzuki, Maria C. Torres, Radha R. Bonala, Francis Johnson, Arthur P. Grollman and Shinya Shibutani
Drug Metabolism and Disposition July 1, 2006, 34 (7) 1122-1127; DOI: https://doi.org/10.1124/dmd.105.008706
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
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
Show more Articles

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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics