824 THE CARCINOGENIC STIMULUS II 



gestation, immediately after birth (Gross, 1950) or later in life. Encouragement 

 can be deriv^ed from alteration of host response to known cancer- producing agents, 

 since otherwise genetic determination would appear to be inevitable. The non- 

 appearance of neoplastic disease {e.g. leukemia) in members of inbred high-leu- 

 kemia stocks indicates the importance of non-genetic influences, perhaps in altering 

 the response of the host to the factors which induce neoplastic disease (MacDowell 

 and Richter, 1935). 



I. HORMONAL FACTORS IN CARCINOGENESIS 



The high incidence in the human population of cancer of the mammary and 

 prostate glands, ovary and uterus suggests the involvement in carcinogenesis of 

 hormones which stimulate normal tissue growth. 



An approach has been made toward an experimental analysis of the hormonal 

 etiology of neoplasms. Experimental neoplasms of the pituitary gland and its 

 target tissues have been induced by altering the reciprocal hormonal relations 

 between the pituitary gland and the organs sensitive to its trophic hormones. In- 

 duced neoplasms of the pituitary and other endocrine glands are considered below. 



[a) Pituitary and thyroid neoplasms induced by alteration in thyroid function 



Tumors of both the mouse (and rat) thyroid and pituitary have been induced 

 by '\ tnmtsteni g radioiodine (Figs. 1-4). If a relatively small amount is given, 

 sufficient however, to interfere with thyroid function, then adenomata may develop 

 (Purves and Griesbach, 1946). Increased stimulation by pituitary thyrotrophic 

 hormone (TSH) is probably a factor in the genesis of such thyroid adenomata. 

 Thyroid carcinoma has developed in the non-stimulated rat thyroid gland fol- 

 lowing administration of '-^'I, suggesting the direct carcinogenic action of ionizing 



PITUITARY TUMORS FOLLOWING HYPOTHYROIDISM 



(3) PITUITARY 

 HYPERSECRETION 



(2) DECREASED ; \ X « INHIBITION OF 



BLOOD LEVEL (4) DEPENDENT PITUITARY NEOPLASIA 



OF THYROID '• PITUITARY BY EXOGENOUS 



HORMONE ', NEOPLASM THYROID HORMONE 



I- 131 \K. y) 15) TRANSPLANTS 



(I) RADIOTHYROIOECTOMY V>-^0' ONLY IN 



^. ^ „ (THIOURACIL, SURGERY, HYPOTHYROID 



rig. I. oequence oi events iodine deficient diet) hosts 



in experimental pituitary (6) transplants 



. . P ,, . , IN INTACT HOSTS 



tumonsrenesis lollowine ny- i ''^' 



^ . ° ' SECRETE TSH^THYROID HYPERPLASIA 



pothyroidism. and neoplasia 



radiation (Goldberg and Chaikoff, 1952). If thyroidectomy is complete, then 

 pituitary tumors develop after a latent period of several months (Gorbman, 1956). 

 Radiothyroidectomy-induced pituitary tumors can be successfully transplanted 

 only into thyroidectomized recipients of appropriate genetic background (Furth, 

 1953). Although the recipient satisfies the usual histocompatibility requirements 

 for transplantation, pituitary tumor transplants will not grow unless the recipients 

 are athyroid. The tumors attain the capacity to grow in intact mice (Fig. 4) after 



