GENETICS OF SOMATIC CELLS 431 



outcrossing one of the parental strains with a third strain. This did not appear 

 possible. Whenever takes obtained in a semi-isologous F 1 were tested further and turned 

 out to be specific variants, they were not specific for the F 1 in question but for the paren- 

 tal strain that entered the outcross. In other experiments, attempts were made to 

 detect the possible occurrence of genetic recombination between different tumor cells 

 by mixing two different, highly specific, F x tumors containing four different H-2 

 markers and growing them together in newborn mice of a fifth H-2 type, not yet capable 

 of an efficient homograft reaction. The mixed tumor was tested in the two original F x 

 types and the four new F 1 combinations in order to select possible genetic recombina- 

 nants. Altogether 24 such experiments were carried out, all with negative results. 

 This excludes the possibility that transfer of genetic fragments between host and tumor 

 cells or among tumor cells might be responsible for variant formation; new, semi- 

 isologous, F x variants would also be expected to appear if this were the case. 



As another possibility, it might be speculated that variant formation could be due 

 to the contact of tumor cells with antibody and subsequent immunologic enhancement. 

 Such enhancement 674 can be induced experimentally by pretreatment of genetically 

 foreign hosts with lyophilized tumor or with isoantiserum, and it empowers certain 

 tumor homografts to grow in otherwise resistant hosts. Such growth may lead to a 

 physiologic 674 change in the tumor, enabling it to grow for several passages in untreated 

 hosts of the same strain, although it dies out eventually as a rule. The question arose 

 whether enhancement, known to be mediated by humoral antibodies, is possibly 

 involved in variant formation. In one series of experiments, animals of one parental 

 strain were pretreated before inoculation by intraperitoneal injection of isoantiserum 

 directed against the opposite parental strain or with tumor supernatant. 716 A total 

 of 20 tumors were inoculated into parental hosts pretreated in this way, but only in 

 10 cases was a clear-cut enhancing effect registered. The enhanced tumors were 

 transplanted further to untreated mice of the same parental strain and to other geno- 

 types. Some of them turned out to be false positives, others were nonspecific, while 

 still others were true variants, specifically compatible with preimmunized mice of the 

 parental strain and capable of breeding true during serial transfer. When considering 

 those neoplasms which could give rise to variants in nonenhanced mice in a certain 

 frequency, it cannot be said that enhancement has facilitated the establishment of true 

 variants to any detectable extent or in any specific way. More significantly, enhance- 

 ment did not seem to promote the formation of any variant that did not also arise 

 spontaneously in a given F x tumor-parental-host system. Neither did it permit the 

 establishment of true variants from homozygous tumors, compatible with a foreign 

 homozygous H-2 genotype, nor of variants from heterozygous tumors, exclusively 

 compatible with a semi-isologous F x type derived from the outcross of one parental strain 

 with a third strain. 



Another attempt was made to check the possible role of enhancement in the 

 establishment and maintenance of variants, by inoculating them into mice of the 

 parental strain preimmunized against the opposite parental strain by a single dose of 



