Effect of Tubercie Bacilli Extracts on Induced Tumors of the Rat

review of the clinical reports, and of animal experi mentation, on the influence of bacterial toxins on malignant tumors, since the method was first used by W. B. Coley in 18992. Beebe and Tracy (92)found that suspensions of Bacillus prodigiosnie, Streplococcn3 pyogenes, Staph ylococcus aurens, and B. coli communis caused regression of large transplanted lymphosarcomas in the dog. Similar results were obtained with bac terial preparations by Uhlenhuth, Haendel, and Steffenhagen (927) on rat tumors. Positive results were obtained only when the material was in jected directly into the tumor. Gratia and Linz (11) found that B. coli filtrates produced hemor rhage and liquefaction in transplanted liposar comas in the guinea pig. Schwartzman and Michailovsky (921) reported the complete disappearance of tumors in mice after injecting meningococcus filtrate. Duran-Reynals (8) used Eberthella typhosus, B. enteriditi@ and B. paratyphosus filtrates and showed that in mice the newly formed tumor capillaries were very sen sitive to these toxins. Apitz (1) studied the hemor rhagic reaction in 197 mouse carcinoma by means of B. coli filtrates and other bacterial substances and concluded that the walls of the tumor capil lanes were damaged. This was not a generalized vascular reaction, but was confined to the tumor capillaries. Shear began in 1933 to fractionate the hemor rhage-producing substance from B. prodigiosus and found it to be a polysaccharide. Following this he (9292)studied the effect of meningococcus @ filtrate and various bacterial metabolites and found that in certain cases liquefaction and hemor rhage of the tumor occurred with an occasional complete regression. He (923) next separated the hemorrhage-producing fraction of the B. coli filtrate and produced extensive hemorrhage in mouse tumors. Severe hemorrhage was produced in subcutaneous primary induced mouse tumors by Shear (924) within a Few hours after injecting the concentrated filtrate from B. prodigiosus in these tumors, but not in the normal tissue. Shear (925) used doses as low as part of a micro gram from the polysaccharide of B. prodigiosus on 750 mice bearing subcutaneous primary tumors, induced by 3,4 benzypyrene, and produced hemorrhage in them within a few hours. Diller (6) found that the polysaccharide of B. prodigiosus, when injected intravenously into a tumor-bearing animal, caused nuclear changes in the tumor cells. These changes involved surface blistering, shrink age, pyknosis, and attenuation of nuclei leading ultimately to their complete destruction. Of special bearing on our problem are the exten sive studies by Morse and Scott (13) on histo logical changes produced in normal animals by the lipoid, protein, and polysaccharide fractions of the tubercie bacillus. Sabin and Doan (16) oh served numerous cellular changes in rabbits after injecting the proteins and phosphatide fractions of human tubercle bacilli and in 1930 Sabin, Doan, and Forkner (17) reported further studies on the reaction of normal rabbit tissues to lipoid, protein, and polysaccharide fractions of Mycobacterium tuberculosum H37. Sabin et a!. (18) found that the polysaccharide may have some killing power under certain conditions, but this is not as consistently related to dosage as in the case of proteins. Smith burn and Sabin (926)showed that the phosphatide fraction stimulates the formation of characteristic epithelioid and giant cells. Schaefer (920)separated the lipoid, polysaccharide, and protein fractions of tubercle bacilli and studied their action on normal mammalian tissues. Delaunay et al. (5) have demonstrated the leucocytic chemotactic power of certain constituents of tubercle bacilli in the guinea pig. It is the purpose of the writers to describe the effect of the protein, phospho-lipoid, and poly saccharide fractions of Mycobacterium tubercu losum on methylcholanthrene-induced tumors in the rat.