Inhibition of growth of Ehrlich ascites tumors in ICR-Ha Swiss mice by isocyanates.

The polymerization of N-carboxyglycine anhydride has been used to identify potential inhibitors of protein synthesis and hence of cancers. Polymerization inhibition was observed wi th N-me thylbis(2.chloroethyl)amine HC1, busulfan, I ,9-dimethylsulfonyloxynonane, phenyl isocyanate, etc. (14), tris(2-chloroethyl)amine HC1 (7), and chiorambudil (G. E. Moos and J. B. Morrison, unpublished data). Isocyanates have been evaluated against cancers, with mostly negative results. l-Naphthyl, 1,5-naphthylene di-, p-ni t rophenyl, p-bromophenyl, hexamethylene di-, p-me t hoxy phenyl , o-e thoxyphenyl, o-chlorophenyl, isopropenyl phenyl, 4-o-terphenylyl, toluene-2,4,6-tri-, p-phenylenedi-, 2,4-m-tolylene di-, and cyclohexyl isocyanates have given negative results against one or more of the following cancers: Sarcoma 180, adenocarcinoma 755, leukemia Ll210, Walker carcinoma 256, and Ehrlich ascites tumor cells (8—13, 15, 17, 19, 20). Water, 0.85% NaCl, Locke-Ringer solution, CMC,2 or methyl cellulose vehicles were used. o-Chlorophenyl isocyanate slightly inhibited the growth of methylcholanthrene-induced sarcoma (25). Butyl isocyanatoacetate reduced the number of takes of Nelson ascites tumors (23). We used peanut oil (22) as a vehicle to protect the isocyanates from hydrolysis. Chloromethyl hydrocarbon derivatives exhibit greater antitumor activities administered in sesame oil than in NaCl suspensions (16). Ehrlich ascites tumors have advantages and disadvantages (18, 21 , 22, 24).