GENETICS OF NEOPLASIA 261 



appear earlier in the breeders than in the virgins. This strain difference was shown 

 to be a genetic difference, and it was suggested that it could be manifested through 

 the control of hormonal production by the ovary or control of the response of the mam- 

 mary gland. Huseby and Bittner 623 transplanted ovaries from strain A and strain 

 G3H subcutaneously into their ovariectomized F-t-hybrid females and observed a higher 

 incidence of tumors among females with C3H ovaries than among those with A ovaries. 

 This result indicated genie action within the ovary that, through the control of hormonal 

 production, eventually influenced the occurrence of mammary tumors. They also 

 transplanted A ovaries into ovariectomized A females so that an A mammary gland 

 stimulated by an A ovary could be compared with the genetically different F 1 mammary 

 gland also stimulated by an A ovary. More tumors occurred in the F x than in the A 

 glands suggesting that the action of some genes was manifested in the host, controlling the 

 response of the mammary gland. 



In testing the effect of the lethal yellow gene on mammary tumors in (C3H x 

 YBR) F 1 females, half of which are yellow (A y /A) and half are black agouti (A/a), it was 

 observed that the effect of A y was to cause the tumors to appear in the virgin yellow 

 females with the same incidence and tumor age as was observed in the breeding agouti 

 females. The tumors also occurred with the same incidence in the virgin agouti 

 females, but at a much later age. Information on the path of action of this specific 

 gene can now easily be obtained by exchange of ovaries between these yellow and 

 agouti F 1 females. 



Endocrine studies suggest that the effect of the ovary on occurrence of mammary 

 tumors is by way of the pituitary gland. The effect of the pituitary gland also has been 

 noted in that the addition of pituitary transplants greatly increases the occurrence of 

 mammary tumors. 916 The pituitary glands can be transplanted subcutaneously, 

 although beneath the capsule of the kidney is probably a more effective site. Proper 

 genetic pituitary-host transplant combinations should reveal whether or not genie 

 action within the pituitary gland is also influential in controlling the occurrence of 

 mammary tumors. 



Transplantation of the mammary gland to obtain glands of different genotypes 

 growing in the same host presents some technical problems, particularly in eliminating 

 the host's own glands so they will not interfere with the transplanted glands. These 

 problems were overcome in part at least by Prehn, 1022 who transplanted rather large 

 portions of the skin with the underlying gland to the backs of females where but little 

 gland normally appears, and he obtained some tumors in the transplanted gland. In 

 so doing, he demonstrated that genie action within the mammary gland governed its 

 response to either the hormonal stimulation, the mammary-tumor agent, or both. 



The most important technique along these lines, however, is that developed by 

 DeOme and co-workers 251 for the transplantation of the hyperplastic nodule of the 

 mammary gland into a cleared fat pad. (See Appendix VII for a description of this 

 technique.) The fact that one is dealing here with a rather small clump of cells, from 

 which the neoplasm arises without interference from the host's own glands, makes such 



