REACTIVITY OF MALIGNANT NEOPLASMS 24I 



of stock mice. These liiulings emphasized the im}x)i'iance of selec- 

 tion of a susceptible stiaiii of mice for studies on the reaction. 



Ander\ont failed to produce hemorrhages in practically all 

 spontaneous mannnary gland carcinomas of mice as well as in 

 the hrst transplants t)f such tumors. Ho\\e\cr. B. coli cidtine fil- 

 trate prochiced hemorrhage Avith regularity in jDrimary 1:2:5:6 

 dibenzanthracene tumors and in some instances brought about 

 complete retrogression of the first transplants of such tumors. 



Later extending their studies, Andervont and Shear purified 

 the acti\ e principles of the phenomenon by the use of the method 

 of Felton, Kauffmann and Stahl already described in Chapter iii. 

 The purification Avas guided by testing the actix ity of each frac- 

 tion on tumor-bearing mice and later also by means of the phe- 

 nomenon in the rabbit. Since Andervont found that different 

 strains of mice reacted some^vhat differently to these principles, 

 regularly reproducible results Avere insured by the employment 

 of a pure strain "M" of mice. For tlie most part, sarcoma 37 was 

 employed as the test tumor although other transplanted sar- 

 comas, as well as primary sarcomas, induced by polycyclic hydro- 

 carbons Avere similarly affected by the active principles of the 

 phenomenon. The Avater soluble fraction obtained by the above 

 mentioned chemical methods A\as highly potent in producing 

 hemorrhage in mouse tumors. The minimum effective dose Avas 

 0.1 c.c. of 1:1000 dilution of a stock solution Avhich contained 22 

 mgms. of the acti\e fraction per c.c. Thus, hemorrhage Avas pro- 

 duced regularly by this dose Avhich contained 0.0022 mgm. of 

 the active material. In an in\estigation comparing the tumor- 

 destroving and phenomenon-producing potencies, these authors 

 found that Avith pinified fraction the phenomenon of local skin 

 reacti\'ity in the rabbit Avas obtained Avith an amount of 0.0005 

 mgm., Avhich is close to the minimal amount (0.003 mgm.) effec- 

 ti\e in elicitation of hemorrhage in the mouse tumor. 



Fogg (1936) obserA'cd that a gram-negative bacillus resembling 

 B. jjiuteus and occurring as a contaminant in cultures of mouse 

 sarcoma 180 made in vitro regidarly produced liquefaction of the 

 explanted tissue. His next series of experiments consisted, then, of 

 studies on the effect of acti\e principles of the phenomenon de- 

 riAed from this microorganism upon mice bearing sarcoma 180. 

 Heat-killed suspensions of bacilli and alcohol-insoluble fractions 

 Avere used. The latter prochu t A\as made in the folloAving manner: 



An alkalinized suspension of bacteria Avas centrifuged, the su- 



