DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy

Sae Hahm, Harley S. Dresner, David Podwall, Michelle Golden, Raz Winiarsky, Mark Moosikasuwan, Antonio Cajigas, Jacob J. Steinberg

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Adriamycin (ADM, or doxorubicin hydrochloride) is an effective antineoplastic agent whose use is restricted by its well-described, dose-dependent cardiotoxicity, This study measures ADM DNA adduct formation by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thinlayer chromatography (2D-TLC), and quantitating the adducts with autoradiography and densitometry. Thirty-six male Sprague-Dawley rats are randomized to receive ADM at varying intraperitoneal (IP) injection concentrations: 0.9% saline IP controls, 4mg/kg ADM IP, and 6mg/kg ADM IP. Myocardial and pulmonary tissues are harvested 48 hours after IP injection for autoradiographic and histopathologic analyses. The results indicate differences in the amount and type of adduct formation as a function of ADM concentration. Increased partial depurination of dGMP and dAMP occurs with increasing ADM concentration at equal incubation times. This depurination correlates with the emergence of new adducts HM-dUMP, 8-OH-dGMP, HM-dCMP, and Me-dCMP. The quantification of these adducts can potentially represent an early marker of ADM cardiotoxicity and thereby optimize the efficacy of individual chemotherapy regimens while minimizing adverse effects.

Original languageEnglish (US)
Pages (from-to)53-67
Number of pages15
JournalCancer Investigation
Volume21
Issue number1
DOIs
StatePublished - Mar 18 2003

Keywords

  • Adriamycin
  • Biomarker
  • Cardiotoxicity
  • DNA adduct
  • Doxorubicin-HCl
  • Hydroxymethyl deoxyuridine monophosphate (HM-dUMP)
  • P-radiolabeling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Hahm, S., Dresner, H. S., Podwall, D., Golden, M., Winiarsky, R., Moosikasuwan, M., Cajigas, A., & Steinberg, J. J. (2003). DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy. Cancer Investigation, 21(1), 53-67. https://doi.org/10.1081/CNV-120016404