DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy

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

doi:10.1081/CNV-120016404

DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy

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

Pathology

Research output: Contribution to journal › Article › peer-review

7 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 language	English (US)
Pages (from-to)	53-67
Number of pages	15
Journal	Cancer Investigation
Volume	21
Issue number	1
DOIs	https://doi.org/10.1081/CNV-120016404
State	Published - 2003

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1081/CNV-120016404

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title = "DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy",

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.",

keywords = "Adriamycin, Biomarker, Cardiotoxicity, DNA adduct, Doxorubicin-HCl, Hydroxymethyl deoxyuridine monophosphate (HM-dUMP), P-radiolabeling",

author = "Sae Hahm and Dresner, {Harley S.} and David Podwall and Michelle Golden and Raz Winiarsky and Mark Moosikasuwan and Antonio Cajigas and Steinberg, {Jacob J.}",

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doi = "10.1081/CNV-120016404",

language = "English (US)",

volume = "21",

pages = "53--67",

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T1 - DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy

AU - Hahm, Sae

AU - Dresner, Harley S.

AU - Podwall, David

AU - Golden, Michelle

AU - Winiarsky, Raz

AU - Moosikasuwan, Mark

AU - Cajigas, Antonio

AU - Steinberg, Jacob J.

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

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KW - Biomarker

KW - Cardiotoxicity

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KW - Doxorubicin-HCl

KW - Hydroxymethyl deoxyuridine monophosphate (HM-dUMP)

KW - P-radiolabeling

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JO - Cancer Investigation

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ER -

DNA biomarkers antecede semiquantitative anthracycline cardiomyopathy

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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