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Actinomycin D in Vivo: Paradoxical and Nonspecific Effects on Adrenal Cortex¹

Unit of Experimental Medicine, Department of Nutrition and Food Science, Massachusetts Institute of Technology Cambridge, Massachusetts 02139

This investigation was aided by American Cancer Society Grants P-372A and P-433 and by an American Cancer Society Faculty Research Associate Award (PRA-22) to the investigator.

Part of this work was carried out in the Division of Endocrinology, Scripps Clinic and Research Foundation, La Jolla, California.

Abstract

Previous, apparently contradictory reports of the effects of actinomycin D on adrenal corticosteroid production encouraged the present investigation of the consequences in vivo of a single administration to guinea pigs of a small dose (10–15 µg/100 g body weight). Within 2 days, base line plasma cortisol levels and urinary corticoids rose, and the effect of exogenous ACTH was curtailed. In the next several days, as base line values fell, the influence of ACTH on plasma cortisol was potentiated. The effect of the antibiotic on RNA synthesis was also biphasic: Synthesis was depressed for 36 hr but then rapidly recovered, so much so that both 32P incorporation into cytoplasmic RNA and the net amount of adrenal RNA rebounded significantly above control levels. These results cannot be regarded as consequences of the inhibition of RNA synthesis by actinomycin, for they were accompanied by net losses of protein and DNA and by histological evidence of cytotoxicity in the adrenal cortex. A review of many of the effects of actinomycin which have been reported by others also indicates that the effects of this inhibitor vary with the cells examined, the dosage, and the timing of observations, and frequently appear to be nonspecific manifestations of toxicity. Extreme caution is called for in using actinomycin as a probe of the molecular biology of hormone action. (Endocrinology 85: 1114, 1969)

Footnotes

¹ Presented in part at the 49th Meeting of The Endocrine Society in Miami, Florida, June 1967.

Received September 12, 1968.