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Cancer Research 



frog Rum* wp. 



Meadow frog Rana nrttetns 



European e<lible frog Ramc t t euttnta 



LeopArd frog Rama fifUns 



Ewopcan edible frog Rama tsetdtnia 



frog JtMM fp. (2) 



frog Rama ip. (2) 



EoropcBB edible frog Rama escmttmta 

 frog JtMMip. 



Ettropean edibte frog iRaiM tumUmta 

 Etiropeu edibk frog Rama tscmUmta 

 Painted Eacueno Ctratapkrys ormala 

 American BuD frog Rama caUsbUmm 

 European edible frog Rama $$€tiUmta 

 Leopard frog Rama fipiams 

 Brown-throated frog Ramafusca (17) 

 Brown-throated frog Rana fusca 

 Leopard frog Rana pipiens (1200) 

 American Bull frog Rana caUsbiana 



Green frog (tadpole) Rana clamitams 



European edible frog Rana tscuUnta 



ipedes. The reports include adenomas in three 

 qpedes, hepatoma in one, carcinoma in four, sar- 

 coma in three, and fibroma, myxoma and chondroma 

 each in one species. 



The more common and up to the present the most 

 extensively studied tumor is the renal adenocar- 

 cinoma of the leopard frog, Rana pipiens (112, 113, 

 114). Over 1200 examples of such tumors have 

 been examined in our laboratory since 1933. The 

 tmnon occur as solitary or multiple ivory-white 

 masses, and may involve one or both kidneys ( Fig. 

 39). The larger growths not uncommonly metasta- 

 size, e^wcially to the liver and lungs (Fig. 40). 

 Histdogically, the majority of the tumors have the 

 appearance of adenocarcinomas (Fig. 42), and are 

 thus representative of the most common variety of 

 cancer in man. The component epithelial cells are 

 atypical and usually much larger and basophilic 

 than normal kidney cells (Fig. 41). Mitotic figures 

 are common. The stroma is scanty and {xwrly 

 vascular. A capsule is lacking and even in very 

 small tumors marginal extensions infiltrate the ad- 

 jacent kidney. In the larger tumors the entire kid- 

 ney b often destroyed. 



In a relatively small group of the tumors, the 

 t^g/peuwaot is leas atypical, and the growths resemble 

 idwiomas rather than adenocarcinomas. But there 

 ■re many gradation, and it to probable that all of 

 these renal tumors are malignant. 



A distinctive characteristic of the frog carcinoma 

 b the frequent presence of acidophilic intranuclear 

 inclusions which in their general appearance are like 



those found in herpes and certain other diseases 

 known to be due to viruses (Fig. 43). In their 

 typical form, they are conspicuous and clearly recog- 

 nizable. It is obvious, however, that there must be 

 developmental stages and the character of these b 

 still a matter of doubt. The inclusions are invariably 

 confined to the cells of the tumors and do not occur 

 in normal renal epithelium, nor in the cells of other 

 organs. Experiments have supported the indications, 

 first given by the presence of the intranuclear in- 

 clusions, that the tumor is in fact very probably 

 caused by a species-specific virus (115). 



Our experience with regard to the occurrence of 

 metastasis b worthy of record. In the first series of 

 158 tumor-bearing frogs no metastases were found, 

 and the conclusion was reached that this cancer, 

 though locally destructive, does not become db- 

 seminated. Yet tumor emboli are frequently en- 

 countered in vascular spaces (Fig. 44). In a second 

 series of 362 additional cases, metastasb was found 

 in 22 frogs; and to date we have observed over 75 

 tumor-bearing frogs with metastasis, nearly all of 

 them in animals with relatively large tumors. This 

 experience emphasizes that large series of animab 

 must be studied before an opinion about the charac- 

 ter of a neoplasm should be expressed. 



The frog tumors have served for many different 

 kinds of experiments, such as manner of growth in 

 the anterior chamber of the eye of homologous and 

 of heterologous sF>ocies (116, 120). By serial trans- 

 plantation the tumor has been maintained for 14 

 generations (176a). It has been transplanted to 



