GENETICS OF SOMATIC CELLS 443 



tumor by its own products, which would make the cells more self-sufficient and less 

 dependent on exogenous stimulators and inhibitors. The biochemical mechanism or 

 mechanisms involved are entirely unknown and their study would appear to be of 

 considerable importance. 



Ascites conversion, cellular adhesiveness, and related characteristics. — When 42 different 

 murine tumors were compared with regard to their ability to grow in the ascitic form, 721 

 it was found that they differed in convertibility, defined as the capacity of tumor 

 cell implanted intraperitoneally to proliferate as suspensions of free cells or clumps of 

 cells, or both, in the peritoneal fluid and to reach there a high absolute level (of the order 

 of 10 8 to 10 9 ) and relative concentration (70 to 90 per cent of all cellular types). Thirty 

 tumors were not convertible under the experimental conditions; this group included 

 all highly differentiated and slowly growing tumors tested. The 12 tumors that proved 

 to be convertible were all rapidly growing and anaplastic. However, there were some 

 rapidly growing and anaplastic tumors in the inconvertible group also, indicating 

 that a high rate of growth or low degree of differentiation, or both, were necessary 

 but by themselves not sufficient conditions for convertibility. 



Among the 12 convertible tumors, 6 could be converted immediately, that is, a 

 suspension of solid-tumor cells gave rise to typical ascites tumors immediately after 

 their first intraperitoneal inoculation. Six other tumors were not convertible in the 

 beginning but could be adapted by prolonged selective transfer of peritoneal exudate 

 containing tumor cells. This gradual conversion was reproducible for a given tumor 

 and has been subjected to closer analysis. 713, 714, 726 The converted line turned out 

 to be different from the original in a stable and irreversible way. Even after having been 

 returned to and carried in the solid form for a long series of prolonged passages (67-98 

 serial transfers with different tumors), the converted sublines maintained their charac- 

 teristic ability to give rise to typical ascites tumors immediately upon their first intra- 

 peritoneal inoculation, while the original sublines, maintained by serial subcutaneous 

 transfer, had to be subjected to a long series of adaptive passage by serial exudate 

 transfer before becoming convertible. Otherwise, these biologically different pairs of 

 sublines were closely similar in microscopic appearance and with regard to their 

 content of nucleic acid. They differed, however, in their ability to metastasize to the 

 lungs. 713, 1057 The adapted line metastasized earlier, more extensively, and in the 

 form of dissociated and widely disseminated free cells, in contrast to the nonadapted 

 line that metastasized at a late stage only, and then in the form of compact intravascular 

 emboli. The adapted line of cells infiltrated the subcutaneous tissue more, exhibited 

 a lower degree of cellular adhesiveness, and had a higher negative electrical charge 

 of the surface. 1031 



As in the cases previously discussed, the question arose about whether the tumors 

 gradually, convertible underwent a process of selection in the course of the serial 

 exudate transfer whereby a preexistent variant fraction, possessing higher ability to 

 become established in the ascitic form than the rest, was merely concentrated or whether 

 this was a case of true cellular adaptation induced by prolonged exposure to the 



