426 GENETICS OF SOMATIC CELLS 



which the tumor has originated may decrease the take percentage in segregating hybrids 

 considerably 20 and in entirely foreign genotypes in which the tumor nevertheless grew 

 if untreated hosts were used, prevent it more or less completely. 715 - 1051, 1237 This 

 reveals the presence of weak isoantigenic differences that can be overridden by tumor 

 growth unless the hosts are preimmunized. It also suggests that a change in the trans- 

 plantability of a tumor across weak isoantigenic barriers may occur in certain instances, 

 not because of an antigenic loss, but rather through a change in the tumor's ability 

 to reach irreversible size in spite of the antigenic difference. 



A case in point is represented by the phenomenon discovered by Barrett and 

 Deringer. 54, 55 These authors found a regular change in the histocompatibility 

 requirements of a mammary carcinoma of C3H origin after passage through F x hybrid 

 mice, derived by outcrossing C3H with another, resistant strain. We have studied 

 the mechanism of this change and the findings indicated 725 that it was not due to the 

 selection of preexisting variant cells with different antigenicity but could be regarded 

 as having been induced by some factor or factors present in the host environment of the 

 F 1 mouse. It appeared that this change did not involve a loss of isoantigens but 

 rather an increased tolerance to certain isoantibodies involved in the homograft 

 reaction. This view was based on the observation that the difference between the 

 original and the altered line disappeared when they were compared in preimmunized 

 F 2 or backcross hybrids. The Barrett-Deringer change has so far been found to occur 

 with weak antigenic systems only and could not be demonstrated for the strong, H-2 

 barrier. 



The question of why certain tumors grow progressively in genetically foreign hosts 

 of the same species while others of similar origin and microscopic appearance do not, 

 is not understood at the present time. Various mechanisms have been held responsible, 

 such as quantitative changes in the relative amounts of certain isoantigens, 456 decreased 

 antigenicity of the tumor cells due to chromosomal changes, 527, 529 and increased 

 resistance against the homograft reaction, due to an increased isoantigenic content of 

 the tumor cells. 354, 588 In a critical study, however, E. Klein 715 has compared the 

 isoantigenicity of two sarcomas induced by methylcholanthrene. They were induced 

 in the same genotype by the same dose of carcinogen and showed a closely similar 

 microscopic picture but differed with regard to their homotransplantability to genetically 

 different hosts. Inocula of the same size were compared for their isoantigenicity in 

 certain foreign genotypes, subsequent to irradiating the cells with a lethal X-ray dose 

 of 15,000 r. The cells were killed in order to prevent their subsequent multiplication 

 which would have induced an important bias by itself, since the homotransplantable 

 tumor can grow progressively in the foreign host while the nonhomotransplantable 

 tumor will regress and the dose and temporal relationships of antigen emission will be 

 quite different. Under such comparable conditions, both tumors provoked approxi- 

 mately the same antibody response as measured by isohemagglutinin formation and 

 by the rejection of a second homograft. Homotransplantability could not be attributed 

 to an increased resistance against the graft reaction either, since the cells of the nonspecific 



