Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
International Journal of Toxicology
This Article
Right arrow Full Text (PDF)
Right arrow References
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by Hollinger, M. A.
Right arrow Articles by Giri, S. N.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Hollinger, M. A.
Right arrow Articles by Giri, S. N.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

In Vitro Uptake and Subcellular Distribution of the Cardiotoxin [3H]Adriamycin in Mouse Ventricle Slices

Mannfred A. Hollinger

Department of Medical Pharmacology and Toxicology, School of Medicine, and *Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, U.S.A.

Shri N. Giri

Department of Medical Pharmacology and Toxicology, School of Medicine, and *Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, U.S.A.

Adriamycin (ADR) is a drug with relatively selective cardiotoxicity. The present study was designed to investigate its distribution into heart subcellular components and correlate such distribution with proposed loci of cardiotoxicity. Uptake of [3H]ADR by mouse ventricular slices was linear for 30 min and plateaued thereafter. The uptake was temperature dependent, being linear from 0° to 45°C. Uptake was also linear over an ADR concentration range of 0.59–8.85 times 10-4 M and increased with wet weight of tissue (25–110 mg). Preincubation with metabolic inhibitors (10-4 M; iodoacetamide and 2,4-dinitrophenol) or 100% N2 failed to affect uptake. Subcellular distribution studies demonstrated preferential localization in nuclei, mitochondria, microsome, and soluble fractions (dpm/µmg protein) in diminishing order, respectively. Therefore, the uptake of ADR by mouse ventricular slices does not involve an energy-dependent transport process and its subcellular localization corresponds with proposed loci of cardiotoxicity.

Key Words: Adriamycin • Cardiotoxicity • Ventricle slices • Subcellular localization.

International Journal of Toxicology, Vol. 15, No. 5, 408-415 (1996)
DOI: 10.3109/10915819609018007
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?