122 Essays in Biochemistry 



and become necrotic. This, also, is the way most tumors behave in 

 the intact animal. 



Cancer cells, then, appear to be members of a race deficient in 

 oxidative mechanisms.""' Their deficiency or immaturity is a permanent 

 inheritable factor. Cytoplasmic inheritance controls differentiation. 

 The mutant we call cancer might well be characteristically deficient 

 in cytoplasmic high energy conversion enzyme systems which are 

 required for differentiation. The different effects of aerobiosis and 

 anaerobiosis could be a reflection of the relative efficiency of the two 

 processes. A 50% difference in oxygen tension such as obtains at an 

 altitude of 20,000 ft. can spell the difference between life and death 

 to an unacclimatized individual. 



The Himalayan expeditions have brought into sharp focus the fact, 

 previously established in the laboratory, that human beings as well as 

 animals, adults at least, can be adapted by suitable acclimatization, 

 not only to survive, but also to do hard work in the rarefied atmosphere 

 of altitudes 20,000 ft. or higher. But when acclimatized animals were 

 implanted with tumors and then returned to high altitude the growth 

 of tumors was markedly inhibited. 9 In many instances the tumors 

 regressed completely, and the animals were permanently cured. It 

 seems as though frustration of either division, growth, or differentiation 

 must lead inevitably to cell death. There is no alternative to com- 

 pletion of these developmental compulsions. It appears to be impos- 

 sible for embryonic cells or tumor cells to revert to resting stages once 

 chromosomal rearrangement for division or cytoplasmic mobilization 

 for growth or differentiation have taken place. A cell is most vulner- 

 able during developmental change, whereas resting adult cells are far 

 more resistant. The widely accepted rule of thumb that cells under- 

 going active mitosis are more sensitive to lethal agents such as X rays 

 than are resting cells is a restatement of the proposition that a cell 

 dies if its division under urgency is blocked. The energy from gly- 

 colysis plus only a modicum of oxidatively generated energy might 

 be sufficient for acclimatized resting host cells but hardly so for vora- 

 cious growing cells. Cancers or other obligatorily growing cells cannot 

 survive partial anoxia; they cannot be acclimatized as can resting cells. 



It does not follow from the above, however, that the cause of cancer 

 is necessarily related to interference with normal oxidative behavior. 

 Mutagenesis is a sine qua non of carcinogenesis. Mutagens are non- 



* This conclusion has been reached before from other considerations. Van R. 

 Potter is well known as an early and active protagonist of the oxidative 1 deficiency 

 hypothesis in cancer. 8 



