Pulst S M, Deen D F
Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143.
Anticancer Res. 1990 Nov-Dec;10(6):1647-50.
Dibromodulcitol (DBD) is an anticancer agent that is cytotoxic against animal and human brain tumors in vivo. Clinical trials of combination therapy with radiation, DBD, and a nitrosourea have shown some efficacy, but the mechanisms that lead to enhanced cytotoxicity are poorly understood. We investigated the effects of pretreatment with DBD on cell survival and sister chromatid exchange (SCE) caused by subsequent treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) in 9L rat brain tumor cells. Pretreatment of 9L cells for 24 hr with 5 microM DBD potentiated the cell kill produced by a 1-hr treatment with BCNU; the dose enhancement ratio was 1.7 at the 10% survival level. Treatment of 9L cells for 24 hr with 1 microM DBD induced 39 +/- 12 SCEs/metaphase. There was a 50-75% increase in BCNU-induced SCEs, compared with BCNU alone, after a 24 hr pretreatment with DBD. Thus DBD potentiation of BCNU cytotoxicity appears to be related to increased DNA damage.
二溴卫矛醇（DBD）是一种抗癌剂，在体内对动物和人类脑肿瘤具有细胞毒性。DBD与放疗及亚硝基脲联合治疗的临床试验已显示出一定疗效，但导致细胞毒性增强的机制尚不清楚。我们研究了用DBD预处理对9L大鼠脑肿瘤细胞随后用1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）处理所引起的细胞存活及姐妹染色单体交换（SCE）的影响。用5微摩尔/升DBD对9L细胞预处理24小时可增强BCNU 1小时处理所产生的细胞杀伤作用；在10%存活水平时剂量增强率为1.7。用1微摩尔/升DBD处理9L细胞24小时可诱导39±12次SCE/中期。在用DBD预处理24小时后，与单独使用BCNU相比，BCNU诱导的SCE增加了50%-75%。因此，DBD增强BCNU细胞毒性似乎与DNA损伤增加有关。
