Many workers have advanccd the hypothesis that normal growth is controlled by a homeostatic balance between growth promoting and growth inhibiting substances present in normal tissue ^(1.2)) Experimental studies on such growth promoting substances ^(3.4.5.6.7)) and on growth inhibiting
substances ^(5.8,9,11.12.13.14.15.16.17.18.19.20.21.22.23.24.25.26)) have long been actively carried out.
In 1958, the senior writer^(27)) extracted from liver of normal mice factors markedly inhibiting growth of the Ehrlich ascites cancer and N-F (Nakahara-Fukuoka) sarcoma Growth inhibiting substances have since been extracted from animal liver, kidney, spleen, pancreas, lung, muscle, skin, testis, uterus and stomach^(28)), human placenta^(29)), animal bone marrow^(30)), animal and human plasma ^(31)), animal and human adrenal cortex^(32.33)) and animal bone^(34)), while tissue growth promoting substances have been extracted from animal liver, kidney, spleen and intestine^(35)), human placenta^(36)), animal adrenal
cortex^(22)), animal bone marrow^(37)) and animal bone^(34)).
There is accumulating evidence that these growth factors are ubiquitously present in the connective tissue of the musculoskeletal system. Rosenstein and Koehler^(38)) recognized a cancer growth inhibiting substance in animal bone marrow, while Kim^(28)) extracted a tissue growth inhibiting substance from animal muscle, Sohn^(30)) tissue growth inhibiting substance from animal bone marrow, Lee^(37)) tissue growth promoting substance from animal bone marrow, and Im^(31)) both tissue growth inhibiting and promoting substances from animal bone. Tier^(19)) suggested that growth promoting substances may be closely related to the so-called inductor, the bone formation inducing substance present in bone, bone marrow, periosteum, cartilage, epiphyseal plate, and fracture Callus^(39.40.41.42.43.44.45.46)).
Recently, Im^(34)) obtained tissue factors by centrifuging the homogenate of animal bone at high speed and by dializing the resulting supernatant. He observed that the non-dializable substance thus obtained inhibited growth of animal transplantable cancer, whereas the dializable substance promoted it. He also observed that the non-dializable substance inhibited mitosis of liver and kidney of normal mice, whereas the dializable substance promoted it. This promoting action gradually declined, or even reverted, as the dosage and the number of days of administration were increased.
The purpose of present study was to extract growth inhibiting and promoting substances from periosteum as a part of our project on various tissues and to observe the effects of these factors on growth of animal transplantable cancer and on mitosis of liver and kidney of normal mice.
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