Spemann^(1)) in 1934, and Murphy Sturm^(2)) in 1934 first proposed a hypothesis that tumor growth possibly takes place when an equilibrium between certain tissue growth promoting and inhibiting substances in the cells is disturbed. Many experimental works dealing with such tissue growth promoting substances^(3 4 5 6 7)) and inhibiting substances^(8.9.10.12.13.14.15.17.18.21.23.24.25.26)) have been reported. Potter^(27)) maintained that certain enzyme which normally controls cell growth can induce abnormal tumor growth when it combines with carcinogenic substances. Miller and others ^(28.29.30.31)) found that when carcinogenic substances such as 4-dimethylaminoazobenzene
are injected into animal tissue they combine with a protein fraction of the host tissue which possibly controls normal cell growth, and make this protein inactive. They believed inactivity of this protein is responsible for an uninhibited cell growth. Paul^(32)) in 1902 believed that cancer growth is the result of disturbance of homeostatic mechanism in the normal cells. Of the workers^(8.11.13.20.22,33.34.25.36)) who studied tissue growth promoting substances, Kelly and Jones^(36)) centrifuged animal liver homogdnate at 15,000 r. p. m. and added ethyl alcohol to its non-cellular supernatant, thus obtained a sediment. They suggested that this sediment can exert promoting effect on mitosis of the cells. They believed that this substance is a nucleoprotein, whereas Shear^(37.38)) believed it is a lipoprotein.
Chin^(39)) in 1958 successfully extracted tissue growth inhibiting substance from normal mouse liver. Since then, his associates extracted tissue growth inhibiting substances from various animal tissues, i.e. liver, kidney, pancreas. spleen, lung, muscle, testis, uterus, stomach^(40)), bone marrow^(42)) and adrenal cortex^(44)). Subsequently, tissue growth promoting substances were also extracted from animal liver, kidney, spleen, intestine^(45)), human placenta^(45)) and adrenal cortex^(44)). Recent report made by Lim^(49)) showed that, both in animals and men, larger amount of tissue growth inhibiting and promoting substances can be extracted from tumor tissues than from normal tissues.
It has also been suggested that tissue growth promoting or inhibiting substance may possess tissue specificity^(3.47.48)), effect of either factor being greater on the same tissue than on the different tissues.
There are a number of reports on tissue growth inhibiting^(42.50)) or promoting substances in bone. Im^(61)) extracted tissue growth promoting substance from animal bone. Lee^(77)) also extracted same substance from animal periosteum. Levandeis^(51)) in 1938 suspected the presence, in bone, of -a substance stimulating osteogenesis. He injected the alcohol extract of bone into the soft tissue of animals in order to obsrve what he called "induction" of bone formation. Annersten(1940)^(52)), Bertelsen(1944)^(53)), Lacroix(1947, 1951)^(57)) and Moss(1958)^(58)) extracted subtances from bone, periosteum, bone marrow and callus. When these substances were injected into animals, heterotopic new bone formation at the injection site was noted. Thev called these substances "inductor," "organizer" or "evocator." Teir^(19)) in 1952 suggested that growth promoting factor could possibly be an
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