Effect of adriamycin on cultured mouse embryo myocardial cells.

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Abstract
Adriamycin (ADM) inhibited the beating of cultured mouse embryo myocardial cells dose- and time-dependently and subsequently lysed the cells. Fifty percent inhibition of beating cell number was observed when cultures were exposed to 430-520 .mu.M ADM for 0.5 h, 70-100 .mu.M ADM for 4 h and 3.5 .mu.M for 36 h. When cultures were exposed to 3.5 .mu.M 3H-ADM, the radioactivity in the cells reached almost the maximum within 8 h, and about 90% was recovered as ADM itself even after 72 h. However, the beating cell number and the beating rate did not appreciably decrease within 8 h, then decreased to 78.5 and 67.1% at 24 h, and 5.6 and 5.2% at 72 h, respectively. Lysis of the cells was conspicuous at 48 h or later. It was also supported with the decrease in cellular proteins and the release of lactate dehydrogenase. These results indicate that ADM stimulates lysis of the cytoplasmic membrane following inhibition of beating. When cultures were exposed to 70 .mu.M ADM for 4 h and then incubated in ADM-free medium, about 50% of ADM in cells was released within 24 h. However, inhibition of beating and lysis of such cells still advanced at about the same rate as in continuously exposed cells. ADM also decreased the cellular adenosine triphosphate (ATP) content in the same fashion as antimycin A, which inhibited beating in advance of ATP reduction. These results suggested that the beating state of myocardial cells is a sensitive and reliable parameter in this system for studies on the cardiotoxicity of ADM. The system may be useful for studies not only on ADM but also on agents having effects on the heart.