The action of radium on cancer cells. I.—Effects of hydrocyanic acid, iodo-acetic acid, and sodium fluoride on the metabolism and transplantability of cancer cells

Abstract

I. The limiting concs. of well-known inhibitors of metabolism, which permit of subsequent recovery of tumor cells, have been investigated. HCN produces primarily an inhibition of respiration which is of the order of 85-95% in concs. from M/1000 to M/500. As a secondary effect of this inhibition of respiration, the aerobic glycolysis of tumor tissue increases to a value approaching that of anaerobic glycolysis. The effect of HCN is completely reversible in all concentrations up to M/20. The primary effect of NaF and iodo-acetic acid is an inhibition of aerobic glycolysis, which increases progressively with increasing concentration. This direct checking of aerobic glycolysis is accompanied by a smaller indirect inhibition of respiration which increases with the time of exposure. Within certain characteristic concs. these inhibitions are reversible after an experimental period of 1 hr. If these limits of conc. be exceeded, these 2 substances produce an ir-reversible damage to tumor cells. This damaging action appears even with concs. which are insufficient to effect a complete or almost complete inhibition of glycolysis. There is a close parallelism between the degree of metabolic recovery and the effect on the viability of the cell as measured by subsequent transplantations.[long dash] II. It is possible to produce experimentally great variations in the susceptibility to radium of cancer cells by acting on the respiratory mechanism of the cell, but not by acting on the glycolytic mechanism. The devices used for acting on the respiratory mechanism were anaerobiosis, HCN and cold. Although all 3 conditions have the same general action of diminishing the functional activity of the respiratory mechanism, their effect on the susceptibility to radium is in opposite directions. Anaerobiosis diminshes, HCN and cold increase the susceptibility to radium. The possible explanations of these results and their bearing on radiotherapy is discussed.