GENETICS OF SOMATIC CELLS 453 



of malignancy. On the other hand, the ability of a line to grow in the completely 

 foreign host whose own normal responses have been influenced in a rather drastic 

 way is not necessarily indicative of true malignancy; it may be just another form of 

 tissue culture. The use of human volunteers does not ameliorate the situation signi- 

 ficantly, since the homograft reaction is an equally serious complication. 



Critical experiments with cells derived from inbred strains of animals leave no 

 doubt that normal cells can change to malignant in tissue culture. On the basis of 

 present evidence, it is impossible, to judge, however, whether this is a frequent or a 

 rare event and what the relationships are between the probability of its occurrence and 

 such factors as the genetic background of the host, its age, the tissue of origin, the cultural 

 environment, and the period of cultivation. Opinions among tissue culturists vary from 

 belief that malignization is a regular event, occurring invariably after prolonged culti- 

 vation of all cell strains of normal origin, to belief that it is highly exceptional. Sur- 

 prising as they are, these ambiguities can be largely attributed to the lack, in most cases, 

 of a suitable animal recipient for the unequivocal testing of malignancy by isotrans- 

 plantation. Frequently, transplantation tests are being done with lines of cells that 

 have not arisen in inbred strains and, if they have, there is often a gap of several years 

 between the origin of the line and the actual test. Absolute genetic identity between 

 two mammalian organisms can perhaps never be achieved 515 except in the case of 

 uniovular twins, but a good approximation is possible by the use of highly inbred 

 strains of mice. 1129 Even with such strains, separation of independently propagating 

 sublines leads to genetic differentiation fairly rapidly, however. For this reason, a 

 line of cells serially propagated may not be fully compatible with mice belonging 

 to the strain in which it originated, if the time interval elapsing between the first 

 explanation and the actual test extends over several years. 



As a good illustration of the dilemma posed, the admirable work of Sanford et al. 

 can be cited. 1151, 1152 A single cell has been isolated from an established strain of 

 cells, originally derived from the subcutaneous tissue of an adult C3H mouse. From 

 the derived clonal culture, different lines of cells were established and propagated 

 serially in vitro. Cells of one line, designated high-sarcoma producing or high, produced 

 sarcomas in 97 per cent of inoculated C3H mice. Cells of another line, designated 

 low, produced sarcomas in only 1 per cent of mice, unless the animals had been previous- 

 ly X irradiated ; if so, almost half of the mice developed sarcomas. This difference 

 appeared during the first year following the separation of the two lines. Tests were 

 designed to investigate whether the cells were antigenically different from the recipient 

 hosts and the X-ray effect could be attributed to the inhibition of a graft response of 

 immunologic nature. It was found that both lines were antigenic to C3H mice and 

 produced cross-immunity against each other. The question arose whether the differ- 

 ence between the high and the low line was really related to the elusive property of 

 malignancy or to a difference in antigenicity. The latter type of difference may con- 

 ceivably develop in one of two ways. Isoantigenic differences may exist between the 

 C3H mouse from which the original cell strain had been derived several years earlier 



