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Effects of Adriamycin on DNA Synthesis in Mouse and Rat Heart¹

Laboratory of Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Adriamycin induces an inhibition of DNA synthesis in mouse tissues within one hr after treatment. While the effects are short-lived in liver and small intestine, DNA synthesis in heart remains below control values for up to 7 days. After this period DNA synthesis in hearts of treated mice is elevated and remains above control values for as long as 4 weeks. Both 1-ß-D-arabinofuranosylcytosine and actinomycin D also induce inhibition of cardiac DNA synthesis soon after treatment; the effects of 1-ß-D-arabinofuranosylcytosine are over by the end of 24 hr while the effects of actinomycin D persist for at least 4 days. Actinomycin D treatment also induces an "overshoot" of DNA synthesis in mouse heart. Adriamycin can induce a loss of prelabeled DNA from heart, although no pathological alterations are immediately obvious. The small intestine, however, shows extensive karyorrhexis. The initial effects on cardiac DNA synthesis occur in adrenalectomized animals, indicating that the effects are not mediated via the adrenal gland. We did find, however, that DNA synthesis in heart was sensitive to the effects of starvation. The results of this study indicate that inhibition of mouse heart DNA synthesis is not specific for Adriamycin and that the effects of Adriamycin in heart following a single treatment are long-lived.

¹ Supported in part by Grants CA 08748 and CA 18856 from the National Cancer Institute, USPHS, and by the Elsa U. Pardee Foundation. A preliminary report has been published (21).

² Dr. Formelli participated in this study as a Visiting Fellow while on leave of absence from Farmitalia Research Laboratories, Nerviano, Milano, Italy.

³ To whom requests for reprints should be addressed, at Laboratory of Pharmacology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, N. Y. 10021.

Received 3/30/78. Accepted 7/ 5/78.