# ANTHRACYCLINE CARDIOTOXICITY: AN IN VITRO MODEL

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1987 · $89,466

## Abstract

Although the anthracyclines, particularly Adriamycin (ADM), have
been shown to be useful in treating a broad spectrum of human
tumors, cardiotoxicity, often leading to fatal congestive heart
failure, remains a serious dose limiting side effect.  In order to
study the mechanism of ADM-induced cardiomyopathy, we
developed a cardiac cell model in which several of the effect of
ADM described in vivo can be simulated in vitro.  Using this
model we found that cardiac-muscle cells accumulate
significantly greater amounts of ADM and undergo increased
cellular damage as compared to cardiac-derived fibroblasts.  This
observation was coupled with our findings that cardiac-muscle and
a number of carcinoma cell types and Friend leukemia cells
preferentially accumulate the mitochondrial localizing dye,
rhodamine 123.   ADM and rhodamine 123 share in common that
they are both positively-charged at physiologic pH.  Our working
hypothesis is that cardiac-muscle, a number of carcinoma cell
types and Friend leukemia cells have similar mechanisms for
enhanced accumulation of and sensitivity of positively-charged
anthracyclines and rhodamines.

Our specific aims are to determine (1) why cardiac-muscle, a
number of carcinoma cell lines and Friend leukemia cells
accumulate high amounts of positively-charged lipophilic
anthracyclines and rhodamines and (2) whether increased
membrane potentials contribute to increased drug accumulation
and sensitivity in these cell types.  The ultimate goal is to
identify mechanisms responsible for differential sensitivity to
anthracyclines in order to prevent or reduce cardiotoxicity while
improving the antitumor effectiveness of known or heretofore
undiscovered anthracyclines and rhodamines.  Using fluorescence
microscopy, laser flow cytometry, high pressure liquid
chromatography (HPLC), clonogenic assays and our computerized
video cardiac cell function analyzer, we plan to investigate
differential cellular accumulation and cytotoxicity of a variety of
anthracyclines, rhodamines, and other related compounds.  Using
a number of modulators of resistance (calcium channel and
calmodulin inhibitors), we plan to identify those with least effect
on chronotropic and inotropic cardiac cell function and maximum
effect on overcoming resistance to anthracyclines and rhodamines
in cancer cells.  By patch clamp technique, we will measure
membrane potentials in cardiac-muscle, carcinoma and ADM-
sensitive and resistant Friend leukemia cells and assess its
importance relative to drug accumulation and chemosensitivity.

## Key facts

- **NIH application ID:** 3174794
- **Project number:** 2R01CA037109-04A2
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** THEODORE J LAMPIDIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $89,466
- **Award type:** 2
- **Project period:** 1983-07-01 → 1990-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174794

## Citation

> US National Institutes of Health, RePORTER application 3174794, ANTHRACYCLINE CARDIOTOXICITY: AN IN VITRO MODEL (2R01CA037109-04A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174794. Licensed CC0.

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