VI 



GENETIC STUDIES 



867 



testicular grafts were made into estrogen-treated Fi hybrids between susceptible 

 and resistant strains, tumors developed only in the grafts derived from the sus- 

 ceptible strain (Trentin and Gardner, 1957). Pulmonary tissue has been grafted 

 into Fi hybrids treated with either urethane (Shapiro and Kirschbaum, 1951) or 

 carcinogenic hydrocarbon (Heston and Dunn, 1951), mammary tissue to deter- 



GENETIC DETERMINATION OF TUMORIGE NESIS 

 IN TARGET TISSUE 



SUSCEPTIBLE PARENT ^^__^ RESISTANT PARENT 



N ~'" / 



^^ F| HYBRID (SUSCEPTIBLE) / 



I CASTRATION-INDUCED 



2. IRRADIATION. CARCINOGEN-INDUCED OR SPONTANEOUS 



3. ESTROGEN -INDUCED 



4. URETHANE OR CARCINOGENIC HYDROCARBON - INDUCE 



Fig. 66. Table illustrating results 

 on genie determination of suscep- 

 tibility to the induction of neo- 

 plasms. In the case of indcution 

 of neoplasms by various means, 

 it appears that the site of gene 

 action is in the target tissue. Fi 

 hybrids between susceptible and 

 resistant strains demonstrate sus- 

 ceptibility. By grafting untreated 

 tissue into F I hybrids, the suscep- 

 tibility of so-called "susceptible" 

 and "resistant" tissue can be de- 

 termined within a common Fi 

 hybrid host. 



mine a similar effect for mammary tumorigenesis (Prehn, 1953) and thymic 

 tissue for irradiation-induced neoplasia (Kaplan et al., 1956a). 



Thus, target tissues of certain hosts may exhibit a neoplastic response to stimuli 

 innocuous to the same, but genetically different tissues of the same species. There 

 is evidence, however, that host factors may modify the intrinsic tissue response 

 (Huseby and Bittner, 1951 ; Heston and Dunn, 195 1). In some situations, such as 

 induction of pituitary tumors by radio-thyroidectomy, tumorigenesis is not strain- 

 limited. Degree of response varies, however, from strain to strain. For example, 

 the application of methylcholanthrene results in the development of skin tumors 

 in all strains of mice, but some are more susceptible than others. 



That the host is not necessary for malignant transformation is demonstrated 

 by the development in vitro of sarcoma cells from fibroblasts (Earle, 1943; Earle 

 and Nettleship, 1943; Nettleship and Earle, 1943). These studies suggest that the 

 environment of tissue culture may provide a carcinogenic stimulus. With the 

 recent developments on clones derived from single cells and propagated on 

 artificial media, precise studies in this area may be anticipated. Since viruses 

 may be propagated in cell culture, their possible relation to malignant transfor- 

 mation in vitro remains to be determined. 



VII. SUMMARY 



Viruses , hormones, chemical carcinogens and ionizing radiations are responsi- 

 ble for the induction of various types of cancer in different species of animals. The 

 wide variety of carcinogenic agents proposes the perplexing problem of common 



Literature p. 870 



