Prajda N, Kralovánszky J, Somfai-Relle S, Gál F, Kerpel-Fronius S
National Institute of Oncology, Budapest, Hungary.
In Vivo. 1988 Mar-Apr;2(2):151-4.
The toxic effect and anti-tumor activity of B-3839, a new molecular combination of pyrimidine antimetabolite 5-fluorouracil (5-FU) with the alkylating agent N-Chloroethyl-N-nitrosourea (BCNU), was compared to that of BCNU and 5-FU given alone and in physical combination. The tumor inhibitory effect of B-3839 was similar to that of BCNU given alone or combined with a low dose of 5-FU in the i.m. Walker tumor model. Furthermore, the bone marrow toxicity of BCNU was not significantly altered by either form of combination with 5-FU. The intestinal side effects, evaluated by measuring the decrease of marker enzyme (thymidine kinase, xanthine oxidase, alkaline phosphatase, sucrase, maltase) activities in isolated enterocytes, were dose-dependent and moderate. A significant, more than 30%, decrease occurred only if BCNU and 5-FU were given simultaneously or as B-3839. The molecular combination of the two drugs does not provide any additional advantage over their physical combination.
将嘧啶抗代谢物5-氟尿嘧啶（5-FU）与烷化剂N-氯乙基-N-亚硝基脲（BCNU）的新分子组合B-3839的毒性作用和抗肿瘤活性，与单独使用及物理混合使用的BCNU和5-FU进行了比较。在Walker肿瘤模型的肌肉注射实验中，B-3839的肿瘤抑制作用与单独使用BCNU或与低剂量5-FU联合使用时相似。此外，与5-FU的任何一种组合形式都不会显著改变BCNU的骨髓毒性。通过测量分离的肠细胞中标记酶（胸苷激酶、黄嘌呤氧化酶、碱性磷酸酶、蔗糖酶、麦芽糖酶）活性的降低来评估肠道副作用，其呈剂量依赖性且程度适中。只有当BCNU和5-FU同时给药或以B-3839形式给药时，才会出现显著超过30%的降低。两种药物的分子组合相比其物理组合并没有提供任何额外优势。
