EFFECTS ON NEOPLASTIC GROWTH 263 



acids in lymphosarcoma (Kit and Greenberg, 1951) and ascites carcinoma 

 cells (Christensen and Riggs, 1952; Tenenhouse and Quastel, 1960) also 

 may constitute a mechanism for growth retardation. 



Neoplastic Growth in Vitro 



When sarcoma fragments are incubated with 0.018 mM bromoacetate 

 for 1 hr and then placed in tissue culture, growth is inhibited by 38%; at 

 0.036 mM the inhibition is 63%, and at 0.072 niM there is no growth 

 (Krontowski et al., 1932 b). lodoacetate is more depressant and complete 

 growth inhibition is seen with 0.01 mM. Transplantability is not impaired 

 until much higher concentrations are reached. It was emphasized that the 

 sarcoma is more sensitive to these inhibitors than are cultures of fibroblasts. 

 Cultures of Earle's strain L cells are also completely inhibited by 0.01 mM 

 iodoacetate (Cailleau et al., 1955). Eagle's KB strain of human carcinoma 

 cells seems to be the most sensitive of all, 50% growth reduction being 

 produced by 0.0022 mM iodoacetate (Smith et al., 1959). The Ehrlich ascites 

 carcinoma is likewise quite sensitive, inasmuch as incubation with 0.05 mM 

 iodoacetate followed by inoculation into mice leads to some depression of 

 subsequent growth (Holzer et al., 1955 c; Holzer, 1956). Parallel inhibitions 

 of glycolysis and growth were observed, leading Holzer to support the con- 

 cept of the necessity of glycolysis for tumor growth. All of these results 

 point to the high sensitivity of neoplastic cells to iodoacetate and at least 

 present the possibility of selective depression of growth in the animal. 



Neoplastic Growth in Vivo 



Harrison and Mellanby (1931) showed that injection of toxic doses of 

 iodoacetate into mice bearing Carcinoma 63 leads to a marked inhibition of 

 glycolysis in the tumor, although subtoxic doses apparently have no effect. 

 Administration of bromoacetate and iodoacetate to mice and rats bearing 

 various tumors leads to interesting but inconsistent results (Krontowski 

 et al., 1933). Implanted adenocarcinoma responds slowly and its growth 

 may be either stimulated or depressed according to the strain used, whereas 

 rat sarcoma is stimulated, and Ehrlich mouse carcinoma is somewhat inhib- 

 ited by doses which are toxic. Some regression of Flexner-Jobling rat car- 

 cinoma and mouse Carcinoma 63 can be observed when iodoacetate is inject- 

 ed subcutaneously or intraperitoneally at doses of 14.5 mg/kg in rats and 

 29 mg/kg in mice 3 times a week (Goldfeder, 1933). When ammonium chlor- 

 ide is given simultaneously to acidify the animals, the results are more favor- 

 able: in 45 mice 8 tumors showed regression and 9 disappeared, and in 29 

 rats 6 regressed and 9 disappeared. Differences between tumors were also 

 remarked by Franks et al. (1934), mouse Sarcoma 180 showing some re- 

 gression but Carcinoma 63 being unaffected by injection of iodoacetate into 



