HORMONAL FACTORS 



839 



hormone (Kirkman and Bacon, 1950). Upon transplantation such tumors are 

 estrogen-dependent (Horning, 1956). The induction by estrogen of neoplasms in 

 tissues other than those whose growth is "specifically" stimulated makes it appear 

 doubtful that the stimulus to normal proliferation is identical with the carcinogenic 

 stimulus (Figs. 29-31). It has been suggested that carcinogenic agents may 

 induce, within the tissues acted upon, "isocarcinogens" which are the more 



I SECONDARY LEUKEMOGENIC EFFECTS OF X- IRR ADIAT ION | 



SUSCEPTIBLE 



(I) 

 THYMECTOMIZE 



|T0 X-RAYS ) 



..O-)— GRAFT "SUSCEPTIBLE' 

 NORMAL THYMUS 



I Q> V THYMECTOMIZE 



OT— GRAFT -RESISTANT" 



/ NORMAL THYMUS IN 



y / EXPERIMENT 



SIMILAR TO I 



NO LEUKEMIA-INDICATES SITE OF 

 GENE ACTION DETERMINING RE- 

 SISTANCE IS IN THYMUS. 



Fig. 33. Induction of mouse 

 thymomas by X-irradia- 

 tion. If a strain susceptible 

 (I) to the induction of thy- 

 momas by X-rays is crossed 

 with a resistant strain (II), 

 the Fi hybrids are suscep- 

 tible. If the Fi hybrids are 

 thymectomized, however, 

 then this susceptibility is 

 nullified since the thymus 

 is the organ which is pri- 

 marily susceptible. In these 

 experiments of Kaplan et 

 al., 1956, the C57BL was 

 the susceptible strain. If thymectomized mice received thymic grafts post-irradiation from 

 the "susceptible" strain, then thymomas developed. Since the thymus itself was not 

 irradiated, it would appear that the irradiation effect was "secondary". A similar result was 

 not obtained if the thymic graft was from the "resistant" strain, demonstrating the genetic 

 determination of susceptibility to this irradiation effect, such genetic susceptibility residing 

 in the thymus per se. From the neoplastic thymus lymphocytes metastasize to the various 

 organs of the body, yielding systemic leukemia. 



GROWTH— INDICATES 

 NEOPLASTIC CHANGE 

 IN GRAFTED THYMUS 

 AND "SECONDARY" 

 LEUKEMOGENIC EFFECTS 

 OF X-RAYS 



immediate stimuli to carcinogenesis (Gardner, 1957). Such agents might be "viral" 

 in nature. The "indirect" effects of irradiation (Kaplan ^f a/., 1955, 1956c) suggest 

 the likelihood that leukemogenic factors may arise in normal tissue post-irradiation 

 (Fig. 33), and that direct action of ionizing irradiation on target tissues is not 

 essential for leukemogenesis. 



That estrogenic hormone was found to induce neoplastic growth experimen- 

 tally in tissues [e.g. mammary, cervix) in which normal hyperplasia is hormonally 

 stimulated was anticipated; but the leukemogenic action of estrogenic hormone 

 and the induction of renal tumors are complete enigmas. Estrogenic and an- 

 drogenic hormone and cortisone all cause hypoplasia of the thymus; of the 

 three groups of compounds only the estrogenic induces neoplasia, the others in- 

 hibiting the development of thymic neoplasms of the mouse (Gardner et al., 1940; 

 Kaplan, 1948; Woolley and Peters, 1953). 



Fig. 31. Testicular tumor (t) induced by exogenous estrogen. Only certain strains of mice 

 are susceptible to the induction of interstitial cell tumors by estrogenic hormone. 

 Fig. 32. Mammary cancer (m) in male mouse of a high mammary cancer strain. Mammary 

 cancers appear spontaneously only in females of this strain. If males receive ovarian trans- 

 plants as in this case (transplant "ot" is in the ear), or are injected with estrogenic hormone, 

 or possess post-castrational estrogen-secreting adenomas of the adrenal cortex, then mam- 

 mary cancer may appear. 



Literature p. S-jo 



