Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds.
Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13.
D000818:Animals; D000970:Antineoplastic Agents; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002330:Carmustine / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D007939:Leukemia L1210 / Q000188:drug therapy*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009604:Nitrosoguanidines / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology
D000970:Antineoplastic Agents; D009604:Nitrosoguanidines; D009607:Nitrosourea Compounds; D013449:Sulfonamides; D014105:Tosyl Compounds; D008769:Methylnitronitrosoguanidine; D002330:Carmustine