Skip to main content
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Carcinogenesis

Glutathione Conjugates of tert-Butyl-hydroquinone, a Metabolite of the Urinary Tract Tumor Promoter 3-tert-Butyl-hydroxyanisole, Are Toxic to Kidney and Bladder

Melanie M. C. G. Peters, Maria I. Rivera, Thomas W. Jones, Terrence J. Monks and Serrine S. Lau
Melanie M. C. G. Peters
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria I. Rivera
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas W. Jones
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Terrence J. Monks
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Serrine S. Lau
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published March 1996
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

3-tert-Butyl-4-hydroxyanisole and tert-butyl-hydroquinone (TBHQ) are antioxidants known to promote renal and bladder carcinogenesis in the rat, although the mechanisms of these effects are unclear. Because glutathione (GSH) conjugates of a variety of hydroquinones are nephrotoxic, and because 2-tert-butyl-5-(glutathion-S-yl)hydroquinone [5-(GSyl)-TBHQ], 2-tert-butyl-6-(glutathion-S-yl)hydroquinone [6-(GSyl)TBHQ], and 2-tert-butyl-3,6-bis-(glutathion-S-yl)hydroquinone [3,6-bis-(GSyl)-TBHQ] have been identified recently as metabolites of TBHQ in the male rat, we investigated the effects of these metabolites in the male rat. At the highest dose tested (400 µmol/kg, i.v.) 5-(GSyl)TBHQ and 6-(GSyl)TBHQ caused 2-fold increases in the urinary excretion of γ-glutamyl transpeptidase and alkaline phosphatase, and pigments arising from the polymerization of metabolites were deposited in the kidney. 3,6-bis-(GSyl)TBHQ (200 µmol/kg) was the most potent of the GSH conjugates tested and produced significant increases in the urinary excretion of γ-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase, and glucose (2-, 2-, 22-, and 11-fold increases, respectively). Alterations in the biochemical parameters correlated with the degree of single cell and tubular necrosis in the S3-M segment of the proximal tubule, as observed by light microscopy. In addition to nephrotoxicity, 3,6-bis-(GSyl)TBHQ increased the bladder wet weight 2-fold and caused severe hemorrhaging of the bladder. The half-wave oxidation potentials of 5-(GSyl)TBHQ and 6-(GSyl)TBHQ were similar to that of TBHQ, whereas the half-wave oxidation potential of 3,6-bis-(GSyl)TBHQ was ∼100 mV higher than that of TBHQ. The TBHQ-GSH conjugates also catalyzed the formation of 8-hydroxydeoxyguanosine, indicating that GSH conjugation does not impair the redox activity of TBHQ. Because some chemicals may induce carcinogenesis by a mechanism involving cytotoxicity followed by sustained regenerative hyperplasia, our results suggest that the toxicity of GSH conjugates of TBHQ to kidney and bladder may contribute to the promoting effect of 3-tert-butyl-4-hydroxyanisole and TBHQ in these tissues.

Footnotes

  • ↵3 To whom requests for reprints should be addressed, at Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, TX 78712. Phone: (512) 471-5190; Fax: (512) 471-5002; E-mail: slav@uts.cc.utexas.edu.

  • Received September 6, 1995.
  • Accepted January 2, 1996.
  • ©1996 American Association for Cancer Research.
PreviousNext
Back to top
March 1996
Volume 56, Issue 5
  • Table of Contents
  • Table of Contents (PDF)
  • Index by Author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)

Sign up for alerts

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research 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.
Glutathione Conjugates of tert-Butyl-hydroquinone, a Metabolite of the Urinary Tract Tumor Promoter 3-tert-Butyl-hydroxyanisole, Are Toxic to Kidney and Bladder
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Glutathione Conjugates of tert-Butyl-hydroquinone, a Metabolite of the Urinary Tract Tumor Promoter 3-tert-Butyl-hydroxyanisole, Are Toxic to Kidney and Bladder
Melanie M. C. G. Peters, Maria I. Rivera, Thomas W. Jones, Terrence J. Monks and Serrine S. Lau
Cancer Res March 1 1996 (56) (5) 1006-1011;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Glutathione Conjugates of tert-Butyl-hydroquinone, a Metabolite of the Urinary Tract Tumor Promoter 3-tert-Butyl-hydroxyanisole, Are Toxic to Kidney and Bladder
Melanie M. C. G. Peters, Maria I. Rivera, Thomas W. Jones, Terrence J. Monks and Serrine S. Lau
Cancer Res March 1 1996 (56) (5) 1006-1011;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

Carcinogenesis

  • Abstract LB-094: Regorafenib and sildenafil interact to kill tumor cells
  • Abstract LB-093: Activation of the FGFR1 signaling pathway by the epstein-barr virus-encoded LMP1 promotes aerobic glycolysis and transformation of human nasopharyngeal epithelial cells
  • Abstract LB-087: A facilitative role for caspase 3 in promoting genetic instability and carcinogenesis
Show more 3

Articles

  • BCL-2 Gene Family and the Regulation of Programmed Cell Death
  • Multiple Roles for the Wilms' Tumor Suppressor, WT1
  • Membership of Awards Assembly
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement