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A Systematic Investigation of the Presence of Growth-inhibitory Substances in Animal Tissues¹

State University of New York at Buffalo, Buffalo, New York, Armour Pharmaceutical Company, Kankakee, Illinois, and the National Cancer Institute, Bethesda, Maryland 20014

A systematic fractionation and screening of 28 different bovine or porcine tissues was carried out in order to investigate whether there are any "growth-regulatory factors" present in normal animal tissues that would cause reproducible inhibition in some of the routinely used in vivo and in vitro assay systems.

Approximately 1140 tissue fractions were tested against two or more transplanted tumors in mice, a total of 1230 tissue fractions were tested in each of five microbiologic assay systems, and approximately 10% of this number were tested for cell culture cytotoxicity. "Confirmed" antitumor activity against the Sarcoma 180, adenocarcinoma 755, or Ehrlich ascites tumors was noted in 14 fractions derived from blood plasma, red blood cells, pancreas, prostate, red bone marrow, and thymus. Significant cell culture cytotoxicity was found in eight fractions from liver, one fraction from lung, and two from pineal glands. A substantial number of tissue fractions showed significant growth promoting and/or inhibitory activities in one or several of the microbiologic assay systems which include Lactobacillus leichmannii, with vitamin B₁₂ or thymidine as the growth-limiting factor, L. arabinosus, grown both aerobically and anaerobically, and Escherichia coli, in a salt-glucose medium. The various tissue fractions demonstrated a great variety of "activity spectra" toward these assay systems.

Several of the tissue fractions that showed significant inhibitory activity in one of the in vivo or in vitro assay systems were further purified by chromatography. Many of the "inhibitors" appear to be proteins by nature, but some are lipids and other small molecular compounds.

¹ This investigation was conducted under USPHS Contracts No. SA-43-pH-1934 and SA-43-pH-3792 (Cancer Chemotherapy National Service Center, NCI, NIH) during the years 1958–1962.

Received 10/ 6/67. Accepted 4/10/68.