772 6. ARSENICALS 



deposition of cell wall material is reduced by 0.1 mM arsenite, as is the 

 respiration, and thus the increased disappearance of glucose is not due to 

 increased oxidation or polysaccharide formation (Christiansen and Thimann, 

 1950 a). Arsenite inhibits the uptake of water by both potato (Hackett 

 and Thimann, 1950) and artichoke (Hackett and Thimann, 1952) tissue, 

 concentrations in the range 0.01-0.03 mM being 50% effective. What part 

 this plays in the growth inhibition, if any, is unknown, i. e., whether it is 

 a cause or a result. It is important to note that these effects are reasonably 

 specific on growth since the tissues are not damaged over the intervals used. 

 The utilization of endogenous amino acids and the synthesis of protein 

 are readily inhibited by arsenite, but again it is impossible to say whether 

 this is primary or secondary. 



CARCINOSTATIC AND CARCINOGENIC ACTIONS 



Arsenite is now occasionally used in myelocytic leukemia and other 

 blood dyscrasias on the basis of an action which is probably only an exten- 

 sion of its propensity to depress hematopoietic tissues, and perhaps depend- 

 ent on a selectivity arising from the more rapid proliferation of these cells. 

 Other types of neoplastic cells may be inhibited experimentally. Cutler 

 and Bradford (1878) first reported the treatment of normal, anemic, and 

 leukemic patients with Fowler's solution. In normals, there was a progres- 

 sive decrease in erythrocytes and leucocytes; in anemics, a temporary in- 

 crease was followed by a fall in the erythrocytes; in leukemic patients, the 

 white count fell from nearly 1,000,000 to 9000 while the erythrocytes went 

 from 3.000,000 to 2,000,000. On the basis of this generally ignored report, 

 Forkner et al. (1937) treated ten patients having chronic myeloid leukemia 

 with arsenite and observed a marked decrease in the white count, the spleen 

 also returning toward normal. Since that time arsenite has been one of the 

 effective suppressive agents in such conditions, but recently is being sup- 

 planted by possibly more specific drugs. Dustin and his collaborators showed 

 many years ago that cacodylate (dimethylarsinite) causes mitotic irregular- 

 ities when injected into animals, and later demonstrated the inhibition 

 of sarcoma growth (Dustin and Gregoire, 1933). Ludford (1936) confirmed 

 this but found the sarcoma cells to be only delayed in mitosis and not 

 killed or prevented from resuming growth. Cacodylate at 2.3 mM in vitro 

 slowly produces mitotic inhibition and there is an accumulation of meta- 

 phases around 24 hr; higher concentrations arrest mitosis at metaphase 

 in tissue cultures without the formation of an equatorial plate. Sarcoma 

 37 in mice is damaged by subcutaneous injections of various arsenicals, 

 particularly^ the trivalent; of 39 trivalents examined, 30 produced some 

 effect (Leiter et al., 1952). Phenylarsenoxide, for example, induced tumor 

 damage in all animals by 24 hr at a dose of 1.5 mg/kg, which is near the 



