On the Origin of Cancer Cells 333 



in "malignancy" in vivo, the rates of growth of the two lines of cells maintained 

 continuously in vitro have remained nearly identical and relatively rapid. Neverthe- 

 less, the metabolism of the two lines of Cancer cells, whose malignancy was deve- 

 loped in vitro, has been found by Woods, Hunter, Hobby, and Burk to parallel 

 strikingly the differences in malignancy observed in vivo, in a manner in harmony 

 with the predications and predictions of this article. 



The metabolic values were measured following direct transfer of the liquid cul- 

 tures form the growth flasks into manometric vessels, without notable alteration 

 of environmental temperature, pH, or medium composition (horse serum, chick 

 embryo extract, glucose, bicarbonate, balanced saline). The values obtained thus 

 accurately represent the metabolism of growing, adequately nourished, pure lines 

 of healthy Cancer cells free of admixture with any other tissue cell type. The 

 anaerobic glycolysis of the high-malignancy line 1742 was Q M Na == 60 to 80, which 

 is virtually maximum for any and all Cancer cells previously reported, including 

 ascites cells 12 " 14 . The anaerobic glycolysis of the low-malignancy line was, how- 

 ever, only one-third as great, Q M N2 = = 20 to 30. The average aerobic glycolysis 

 values for the two lines were in the same order, Q M ° 2 == 30 and 10, respectively, 

 but of lower magnitude because of the usual, pronounced Pasteur effect, greater 

 in line 1742 than in line 2049 (Q M N ' 2 — Qm° 2 == about 40 and 15). On the other 

 hand, the rates of oxygen consumption were in the converse order, being smaller in 

 line 1742 (Qo 2 == 5 to 10) than in line 2049 (Q . 2 == 10 to 15), corresponding to 

 a greater degree of respiratory defect in line 1742. The respiratory defect in both 

 lines was further delineated by the finding of little or no increase in respiration 

 after the addition of succinate to either line of cells, in contrast to the considerable 

 increases obtained with virtually all normal tissues 9 ; and the respiratory increase 

 with paraphenylenediamine was likewise relatively low, compared with normal 

 tissue responses. 



A further notable difference between the two cell lines was the very much lower 

 inhibition of glycolysis by podophyllin materials (anti-insulin potentiators) ob- 

 served with line 1742 compared with line 2049 (for example, 10 and 70 percent, 

 respectively, at a suitably low concentration). This result would be expected on the 

 basis of the much greater loss of anti-insulin hormonal restraint of glucose meta- 

 bolism, at the hexokinase phosphorylating level, as the degree of malignancy is 

 increased, just as was reported for a spectrum of solid tumors 14 . 



Finally, the high-malignancy line 1742 cells have been found by A. L. Schade 

 to contain 3 times as much aldolase as the low-malignancy line 2049 cells (11, — 

 300 versus 3700 Warburg activity units per milliliter of packed cells extracted), 

 and about 2 times as much «-glycero-phosphate dehydrogenase [2600 versus 1400 

 Schade activity units 13 per mililiter of packed cells extracted]. The potential signi- 

 ficance of these indicated enzymic differences in relation to the parallel glycolytic 

 differences, measured with aliquots of the same cell cultures, is evident, and may 

 well be connected with the corresponding hexokinase System differences. 



The new metabolic data on the two remarkably contrasting lines of Cancer cells, 

 which originated from a single, individual cell and have been maintained exclusively 

 in vitro over a period of years, epitomize and prove finally the main conclusions of 



