304 Conditions for Tumorigenesis 



with the ovary, such as fragmentation or transplantation. Frequent prolifera- 

 tion of uterine glands occurred, with formation of polyps and penetration of 

 glands between the muscle layers of the myometrium, and on one occasion a 

 papilloma of precancerous aspect with pearl formation and cornification in 

 the cerviv apjjeared. Similar observations have been reported for the rat by 

 Pfeiffer." Schmidt"" has reported induction of uterine fibroids by ovarian irra- 

 diation in guinea pigs; here also a protracted action of follicular hormones 

 seemingly plays a role. 



Gonadal fragmentation or transplantation is likely to produce a disturbance 

 of the ovarian-prehypophysial relationship which manifests itself in an in- 

 crease of gonadotrophic substances in the anterior lobe (Lipchiitz"*). It is in 

 this way that the protracted follicular phases which establish themselves under 

 these experimental conditions can be explained. And it is probably by the 

 increased gonadotrophic activity of the anterior lobe that some phenomena of 

 atypical epithelial proliferation in the gonadal fragment or graft itself must 

 be explained. When ovarian fragments or grafts are made, proliferation of 

 epithelial cords in the hilum of the ovary have been reported, though rarely 

 (Lipschutz"'"^). Nodular proliferation of interstitial cells* as observed years ago 

 in testicular fragments (pi. 3, figs. 10 and 1 1) may be explained today on similar 

 lines (Lipschutz"*™'^). This may also apply to the metastasizing interstitial- 

 cell tumor of the testis produced in mice subjected to a prolonged treatment 

 with estrogens (Hooker, Gardner and Pfeiffer'"). 



Summary 



The question is discussed whether the atypical proliferations induced by estro- 

 gens are to be considered as true neoplasms. 



According to the author and his associates, atypical proliferation of epithe- 

 lial and connective tissue elicited by estrogens in the guinea pig affords char- 

 acteristic signs of neoplastic or tumoral growth. Endometrial proliferation 

 with production of squamous epithelium in the uterine mucosa is strictly 

 insular. Adenomatous polyps, with occasional precancerous changes, are pro- 

 duced. Finally, uterine and extragenital abdominal fibroids of typical localiza- 

 tion are formed which infiltrate neighboring tissues. 



There is also a far-reaching similarity betiueen conditions for tumor forma- 

 tion from estrogens and carcinogenic hydrocarbons: (1) The tumorigenic 

 minimum quantity of estrogens is minute under certain experimental condi- 

 tions, especially when the estrogen is enhanced by esterification or when it is 

 absorbed from subcutaneous pellets, though the quantity is still greater than 

 that required of carcinogenic hydrocarbons. (2) The fundamental timing con- 

 dition for the tumorigenic action of estrogens is cojitinuous application of a 

 minimum stimulus. The same seems to be true for carcinogenic hydrocarbons. 



* Twenty years ago this behavior of the interstitial tissue in testicular fragments was ex- 

 plained as due to local conditions, especially those of blood supply (Lipschiitz,"" p. 135). The 

 veering of opinion in this minor case reflects the fundamental change which has taken place 

 in the last two decades in interpretation of physiological and pathological processes. 



