25H PHYSIOLOGIC GENETICS 



PATHS OF GENIC ACTION IN NEOPLASIA 



No characters provide more interesting complex problems in physiologic genetics 

 than do neoplasms. The late occurrence of most neoplasms allows nearly the whole 

 lifetime of the animal for the primary action of many genes to influence the occurrence 

 of the tumor through a multitude of physiologic pathways. All neoplasia involves 

 physiology of growth and differentiation. Physiology of hormonal production and of 

 response to hormonal stimulation is involved in many. When viruses and other 

 parasites are involved, there is the whole field of host-parasite relationship with not 

 only the action of the genes of the host but also those of the parasite to be considered. 

 When the etiologic factors include exogenous physical and chemical carcinogens, there 

 is the physiology of cellular response to these carcinogens. In all of these areas genie 

 action can be involved. 



LOCALIZATION OF GENIC ACTION IN ORGANS AND TISSUES 



One of the most fruitful approaches to the localization of the genie action and the 

 paths through which it influences the occurrence of the neoplasm is through the trans- 

 plantation of tissues and organs of one genotype into hosts of another. This can be 

 done when the donor and the host differ by certain genes but have no conflict in respect 

 to the histocompatibility genes, or when tolerance has been induced in the host. It 

 should be empasized, however, that an animal of one strain made tolerant to tissues 

 from another strain has had its physiology altered. 



Often the F x hybrid is the more convenient host to use and satisfies the require- 

 ments for the experiment. Since the F x has all the dominant genes of both parental 

 strains, organs or tissues from both parental strains and thus of different genotypes can 

 be compared while growing in the common F x host. Thus, genie action or paths of 

 genie action localized within the tissue or organ can be identified. On the other hand, 

 by outcrossing one parental strain to a number of strains, tissues or organs of the same 

 genotype from this strain can be transplanted into the F x hosts of a number of genotypes. 

 In this way genie action can be identified with the host. 



Another advantage of using the F a as host is that one can readily determine 

 whether or not the neoplasm has arisen from the transplant or from host cells. If it 

 arises from the transplant, it is readily transplantable back to the strain of origin, 

 whereas if it arises from the cells of the F x host, it is not ordinarily transplantable to the 

 parental strain. 



This method of approach was applied to the problem of pulmonary tumors in 

 mice 567 (figure 37). In earlier studies 557 it had been estimated that the high pul- 

 monary-tumor strain A differed from the low pulmonary-tumor strain C57L by at least 

 four pairs of genes affecting the occurrence of this neoplasm. The question to be answered 

 was, were these genes becoming manifest within the lung or through some other 

 systemic mechanism? Portions of lung from A mice were transplanted with a trocar 



