III. THE DEVELOPMENT OF CANCERS 363 



frequently takes origin from one or another of them. Tar cancers 

 usually come about by successive, step-like deviation from the normal, 

 and so also do the cancers which derive from virus-induced papillomas 

 as well as many human cancers. After cells have become cancerous 

 they frequently undergo further changes, some apparently step-like in 

 character, and all taking the direction of greater malignancy. 



Sexual hormones may presumably play a role at the last stage of 

 such step-like deviation, although most carcinogens are in themselves 

 closely related to sexual hormones in the chemical structures. It has 

 been stated that acute fowl pox develops in practically every bird 

 painted with methylcholanthrene, one of the well known carcinogenics ; 

 if one continues to paint the bird with this carcinogen, chronic 

 inflammatory reactions develop, as well as angiomas and discrete, 

 poliferative, epithelial lesions. Upon inoculation of the bird with 

 testosterone, a sexual hormone, all of the lesions flare up and the 

 epithelial growths become squamous-cell carcinomas (45). 



Further, if a single application of 3,4-benzpyrene, a carcinogen, is 

 made to the skin of mice, it does not induce cancer, but if the single 

 application is followed by repeated treatment with croton oil, then 

 tumours develop (46) (47). The croton oil treatment alone will not 

 induce tumours. Cholestrol exhibits a similar accelerating effect ; in 

 contrast to croton oil, cholesterol itself has a feeble carcinogenic ac- 

 tivity (48). In such a case, croton oil and cholesterol may behave like 

 sexual hormones. 



Greenstein (49) believes that carcinogens lower the threashold of 

 spontaneous malignancy in the tissues, so that malignant growth is 

 brought about by the sexual hormones, which as such are not carci- 

 nogen. There are numerous evidences showing that estrogens enhance 

 the development of mammary tumour of mice. The inhibitory effect 

 of testrosterone in this connection is also well known. According to 

 Kirkman and Bacon (50) male golden hamsters will produce almost 

 constantly renal cortical cancers if they are treated with estrogen. 



If cancer cells are produced by the structural reduction of somatic 

 cells, and if the structural change of the protoplasm is reversible, 

 cancer cells must return to the original, differentiated structure as 

 do germ, cells. In fact this seems actually the case. Thus, if renal 

 carcinoma of the frog, Rana pipiens, is transplanted onto the base of 

 the fore limb of a newt, and the greater part of the limb being cut 

 off, when the cancer cells begin to multiply, leaving some of the cells 

 in the tissue of the newt, then the cells are changed to normal frog 

 cells during the regeneration of the limb. The frog cells can be easily 

 detected owing to the small size of the nucleus (51). Thus the return 

 of the cancer cells to their original state is established under the 



