314 BIOLOGY OF THE LABORATORY MOUSE 



same hormone failed to prevent the occurrence of mammary tumors in 

 females, or in males treated with estrogen (49). 



Cancerous lesions in or near the cervix have been reported following the 

 injection of estrogens (45, 56, 82, 29). One of these tumors was grafted 

 into young male and female mice in which it continued to grow without 

 further hormone administration (29). Lesions of the cervix similar to 

 malignant tumors appeared in mice receiving estrogen and 1:2:5:6 dibenz- 

 anthracene (74, 73). 



Hemorrhagic chromophobe adenomas of the pituitaries developed in 

 mice following long continued injections of estrogen or its cutaneous appli- 

 cation (17, 18, 12). Hypophyseal tumors did not appear in six inbred 

 strains following the injection of several estrogens for prolonged periods. 

 In another strain 15 of the 106 mice treated showed pituitary enlargement 

 with the largest (46 to 87 mg.) consisting largely of adenomas of non- 

 glandular chromophobe cells (33). 



Two sarcomas were observed among 16 castrated male mice bearing 

 ovarian grafts (21). There have been many reports of sarcomas developing 

 in mice following the injection of estrogens, usually estrogens in oil (15, 32, 

 27, 81, 46). In some cases they developed in relation to the oil cysts. 

 Lymphoid leukemia and lymphosarcomas have been observed in a number 

 of strains following the injection of estrogens while none of the controls 

 have shown such tumors (27, 47, 31). 



The effect of estrogens in conjunction with carcinogenic agents has been 

 investigated. Reviews of the early studies are available (28, 14). 



Hormones and transplantable mouse tumors. — In 1932 Zondeck, Zondek 

 and Hartoch (88) reported an inhibition of growth of the Ehrhch mouse 

 carcinoma following the administration of an extract containing both Prolan 

 A and Prolan B. Using over 400 mice the authors found that the average 

 tumor growth in animals treated over a three week period was 0.2 grams 

 while the control tumors averaged 1.65 grams. Furthermore, it was found 

 that this reduction in growth persisted during later transplants. Many 

 workers have attempted to modify the growth of transplanted sarcomas and 

 carcinomas with pituitary hormones since that time. Some studies con- 

 firmed retardation of growth (13, 66, 6). Some reported stimulation (23, 24, 

 79) and others found no effect upon the growth (36, 39). One of the most 

 serious hazards in such experiments is the difficulty in differentiating the 

 direct and the indirect effects of Prolan on the tumor growth (5). The 

 transplant has been exposed directly to Prolan extract in vitro following 

 which it was inoculated into the host. No evidence of inhibition or accel- 



