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The Human Tumor-Egg Host System

III. Tumor-inhibitory Properties of Tenuazonic Acid^*

( Merck Sharp & Dohme Research Laboratories Division, Merck & Co., Inc., Rahway, N. J.)

The fermented broth of a culture of Alternaria tenuis auct. inhibited the growth of the human adenocarcinoma (H.Ad. #1) in the embryonated egg. With the aid of studies in the egg-tumor system the active agent was isolated and identified as tenuazonic acid. Tenuazonic acid was produced by a number of Alternaria isolated and by an Aspergillus tamarii and a Phoma sp. Compared with tenuazonic acid, on a molar basis, about 20 times as much hadacidin or 6-mercaptopurine, 2 times as much azaserine, but only 1/20 as much triethylenemelamine (TEM) were required to achieve the same inhibition of H.Ad. #1 tumor growth in the egg. Tenuazonic acid was more effective against H.Ad. #1 than against another transplantable human tumor, A-42. Tenuazonic acid, compared with puromycin, more specifically inhibited tumor growth in the egg-tumor system.

^* This investigation was supported, in part, under National Institutes of Health Contract No. SA-43-pH-3057, by the Cancer Chemotherapy National Service Center, National Cancer Institute, Department of Health, Education and Welfare, U. S. Public Health Service, Bethesda, Md.

Received 9/14/63.