The Reaction of Mice and of Various Mouse Tumors to the Injection of Bacterial Products

Abstract

Bacterial products have been used in the treatment of malignant growths since 1882. The literature pertaining to this subject has been reviewed recently by Shear (1). Interest in the problem appears to have been revived by the work of Gratia and Linz (2), who observed that intravenous injection of the filtrate of a broth culture of B. coli into guinea-pigs bearing a transplanted liposarcoma elicited hemorrhage and necrosis within the tumor. Shwartzman and Michailovsky (3) used “agar washings filtrate of meningococcus 44 D group I” and produced the reaction in mouse sarcoma 180. Their results were confirmed in this laboratory (4). Apitz (5) produced hemorrhagic reactions in the Ehrlich mouse carcinoma by injecting B. coli filtrates. Duran-Reynals (6) also employed filtrates of broth cultures of B. coli and produced hemorrhage in 4 transplantable tumors of mice and in a transplantable rat tumor. His filtrate failed to elicit the reaction in animals with certain other types of growth, among which were “19 mice bearing spontaneous malignant mammary gland adenocarcinoma.” Similar negative results with spontaneous mouse tumors were obtained in this laboratory after injection of meningococcus filtrates (7). In a later paper Duran-Reynals (8) describes positive reactions as well as some recessions in spontaneous mouse tumors following treatment with a mixture of filtrates of human typhoid bacillus and 3 strains of mouse typhoid bacilli. Shwartzman (9) has reported recently that a mixture of B. typhosus culture filtrate with homologous antisera produced hemorrhage followed by the complete regression of sarcoma 180 in 21 of 27 treated mice. Fogg (10) has shown that the hemorrhagic reaction and, in many instances, complete retrogression of mouse carcinoma 63 and mouse sarcomas 180 and 37 occurred following the injection of heat-killed cultures of a Gram-negative bacillus belonging to the proteus group. Spontaneous mouse tumors were affected but not destroyed. Furthermore, the alcohol-insoluble fractions of B. proteus, B. typhosus, B. coli, B. pyocyaneus and B. prodigiosus invoked hemorrhage and recession of mouse sarcoma 180. The present paper is a report of further investigations into the problem that have been carried out in this laboratory. It deals with the results of studies pertaining to (1) the toxicity of the bacterial filtrates for mice; (2) the use of cutaneous tumors as test objects for activity of the filtrates; (3) results attending the use of pure strain and stock mice; (4) the effect of filtrates upon different kinds of malignant growths.