260 PHYSIOLOGIC GENETICS 



identity was established early. Fetal lung offers an additional advantage in that the 

 transplanted lobe grows until it forms a mass approximating the size of a lobe of an 

 adult lung, and this provides more tissue in which tumors can develop. The pro- 

 cedure of making a pulmonary tissue mash and treating it in vitro with a carcinogen 

 before inoculating it into the host as Smith 1225 and Rogers 1070 have done, could pro- 

 bably also be incorporated into such genetic studies to link mechanisms of action of 

 the carcinogen with mechanisms of the genetic effects. 



Similar transplantation procedures have been employed in localizing genie action 

 in the etiology of other types of neoplasms. Trentin and Gardner 1331 transplanted 

 testes from newborn susceptible strain A and resistant strain C3H males into castrated 

 adult (C3H x A) F x hybrid males. The transplants were placed at the base of the tail 

 through a subcutaneous tunnel extending from an incision in the scapular region. 

 Two weeks later a 7-mg. pellet containing 25 per cent stilbestrol in cholesterol was im- 

 planted subcutaneously in each host to induce the interstitial-cell tumors in the testes. 

 Tumors arose in a much higher incidence of testes from the strain A than in those from 

 the strain C3H, indicating that genie action determining susceptibility to estrogen- 

 induced testicular tumors resides largely in the end organ. 



Huseby and Bittner 622 transplanted adrenal glands from strain A, which shows 

 minimal postcastrational adrenal hyperplasia, strain C3H, which shows considerable 

 hyperplasia, and strain CE, which develops carcinoma, into the F x hybrids of the various 

 combinations of these three strains. The hosts were then gonadectomized and the 

 adrenal response was observed. The results indicated that the genotype of the end 

 organ determined whether or not this response would be carcinoma, extensive hyper- 

 plasia, or very little hyperplasia. 



Experiments of transplanting thymuses by Law and Potter 765, 769 and by Kaplan 

 and co-workers 684 from susceptible and resistant parental strains to the F x hybrid, 

 indicated genie action within the thymus controlling whether or not leukemia occurred. 

 However, when transplantation of the leukemias was attempted, it was found that 

 some of these occurring late were not transplantable back to the susceptible parental 

 strain, although they were transplantable to others of the F x hybrids. Further observa- 

 tions by Law and Potter that the original lymphocytes of the thymic transplant were 

 gradually replaced by lymphocytes from the F 1 host, confirmed that these tumors were 

 of F 1 origin, and indicated that the important genie action was within the stromal cells, 

 somehow controlling whether or not the lymphocytes became neoplastic. 



The genetics of mammary tumors is more complex, but certain facets of the 

 problem can be approached through transplantation procedures, particularly those 

 related to hormonal influence. In all mammary-tumor strains of mice, hormonal 

 influences resulting from the females' having litters increase the incidence of mammary 

 tumors, decrease the tumor age, or do both. The extent of the observed effect is 

 governed by the genotype of the strain. In strain A mice the virgins have a very low 

 incidence of mammary tumors, whereas the incidence in the breeders is relatively high. 

 In strain C3H the incidence is high in both the breeders and virgins, but the tumors 



