Levels of N7-(2-hydroxyethyl)guanine as a molecular dosimeter of drug delivery to human brain tumors
Levels of N7-(2-hydroxyethyl)guanine as a molecular dosimeter of drug delivery to human brain tumors
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DOI：
10.1093/neuonc/3.4.241
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发表时间：
2001-10-01
期刊：
影响因子：
15.9
通讯作者：
Levin, VA
中科院分区：
文献类型：
--
作者：
Bodell, WJ;Giannini, DD;Levin, VA
采用高效液相色谱-电化学检测法测定了1，3-双（2-氯乙基）-1-亚硝基脲（BCNU）处理人脑肿瘤组织后DNA烷基化产物N7-（2-羟乙基）鸟嘌呤（N7-HOEtG）的含量。来自6名复发性化疗初治的复发性多形性胶质母细胞瘤患者的肿瘤作为对照进行分析。这些标本DNA中N7-HOEtG的平均水平为0.42 pmol/mg DNA。样本也从一名复发性多形性胶质母细胞瘤患者中获得，该患者在用BCNU乙醇溶液（DTI-015）进行直接瘤内治疗后复发。在注射部位远端、中间和附近的样本中，N7-HOEtG水平分别为0.8、2.6和369.5 pmol/mg DNA。远端检测到的N7-HOEtG水平的比较。样品在乙醇中注射BCNU后的平均水平，未处理样品的平均水平表明其差异不足以排除为偶然发生。将内侧和相邻脑肿瘤样本中的N7-HOEtG水平与对照样本的平均水平进行比较，结果显示数值分别高出约6倍和879倍。这些结果表明，BCNU在乙醇中的瘤内给药产生显着水平的DNA烷基化，并表明DNA加合物的测量提供了一个独特的分子剂量计，以评估交付的烷化剂脑肿瘤。
The level of N7-(2-hydroxyethyl)guanine (N7-HOEtG), one of the DNA alkylation products formed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment, was measured in human brain tumor samples by high performance liquid chromatography with electrochemical detection. The tumors from 6 recurrent chemotherapy-naive patients with recurrent glioblastoma multiforme were analyzed as controls. The mean level of N7-HOEtG in DNA of these specimens was 0.42 pmol/mg DNA. Samples were also obtained from a patient with a recurrent glioblastoma multiforme after direct intratumoral therapy with BCNU in ethanol (DTI-015). The levels of N7-HOEtG in the samples distal, medial, and adjacent to the site of injection were 0.8, 2.6, and 369.5 pmol/mg DNA, respectively. Comparison of the level of N7-HOEtG detected in the distal. sample after injection with BCNU in ethanol,with the mean level of the untreated samples indicated that it was not sufficiently different to be ruled out as a chance occurrence. Comparison of the levels of N7-HOEtG in the medial and adjacent brain tumor samples with the mean level of the control samples showed values that were approximately 6- and 879-fold higher. These results demonstrate that intratumoral administration of BCNU in ethanol produces significant levels of DNA alkylation and suggest that DNA adduct measurements provide a unique molecular dosimeter to evaluate delivery of alkylating agents to brain tumors.