Bodell W J, Morgan W F, Rasmussen J, Williams M E, Deen D F
Biochem Pharmacol. 1985 Feb 15;34(4):515-20. doi: 10.1016/0006-2952(85)90182-0.
9L Rat brain tumor cells were treated with 0.2 microM 6-thioguanine for 48 hr, which produced a 40% cell kill, a small (15%) inhibition of cell growth, and an accumulation of cells in S-phase. Maximum incorporation of [14C]6-thioguanine into cellular DNA occurred after 24 hr of incubation; 70% of the label was incorporated into DNA as 6-thio-2'-deoxyguanosine. Pretreatment of 9L cells for 48 hr with 0.2 microM 6-thioguanine potentiated the cytotoxicity of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) by 50% with a dose enhancement ratio of 1.5, and caused a 30% increase in the number of BCNU-induced sister chromatid exchanges (SCEs) and a 50% increase in DNA crosslinks formed, compared to treatment with BCNU alone. Used as a single agent, 6-thioguanine induced a significant number of SCEs. Results suggest that these effects may be related to the increased formation of DNA crosslinks, possibly as the result of the formation of S6-(2-chloroethyl)-6-thioguanine in cellular DNA.
用0.2微摩尔的6-硫鸟嘌呤处理9L大鼠脑肿瘤细胞48小时，导致40%的细胞死亡、细胞生长受到轻微（15%）抑制以及细胞在S期积累。[14C]6-硫鸟嘌呤在孵育24小时后最大程度地掺入细胞DNA；70%的标记物以6-硫代-2'-脱氧鸟苷的形式掺入DNA。用0.2微摩尔的6-硫鸟嘌呤对9L细胞进行48小时预处理，可使1,3-双（2-氯乙基）-1-亚硝基脲（BCNU）的细胞毒性增强50%，剂量增强比为1.5，与单独使用BCNU相比，BCNU诱导的姐妹染色单体交换（SCE）数量增加30%，DNA交联形成增加50%。作为单一药物使用时，6-硫鸟嘌呤诱导了大量的SCE。结果表明，这些效应可能与DNA交联形成增加有关，可能是细胞DNA中形成S6-（2-氯乙基）-6-硫鸟嘌呤的结果。
