Miyahara M, Nakadate M, Miyahara M, Suzuki I, Ishidate M, Odashima S
Gan. 1977 Oct;68(5):573-80.
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.
对聚亚甲基双（1-亚硝基脲）、聚亚甲基双（1-亚硝基-3-硝基胍）和聚亚甲基双（1-亚硝基对甲苯磺酰胺）衍生物进行了抗大鼠腹水肝癌AH-13和小鼠白血病L-1210的抗肿瘤作用测试。双亚硝基脲对AH-13和L-1210有效，双亚硝基胍仅对AH-13有效，而双亚硝基甲苯磺酰胺对这两种肿瘤细胞系均无效。在所有这些化合物中，1,1'-亚乙基双（1-亚硝基脲）（EBNU）最为有效。将EBNU的抗肿瘤作用与1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）的抗肿瘤作用进行了比较。按照L-1210腹腔接种后第1天、第1天和第5天以及第1天、第5天和第9天的给药方案腹腔注射EBNU，结果显示宿主存活时间显著延长，尽管所用的有效剂量比BCNU达到类似效果时所用剂量高出几倍。EBNU对AH-13细胞的最小有效剂量（MED）估计为1 mg/kg，这比BCNU的最小有效剂量低10倍，表明EBNU对AH-13的效果比BCNU更好。
