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接受顺铂和卡铂化疗的头颈癌患者体内的铂-DNA加合物

Platinum-DNA adduct in head and neck-cancer patients receiving Cisplatin and Carboplatin chemotherapy.

作者信息

Parker R, Dimery I, Dabholkar M, Vionnet J, Reed E

机构信息

NCI,MED BRANCH,MED OVARIAN CANC SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. MD ANDERSON CANC CTR,HEAD NECK & THORAC MED ONCOL SECT,HOUSTON,TX.

出版信息

Int J Oncol. 1993 Aug;3(2):331-5. doi: 10.3892/ijo.3.2.331.

DOI:10.3892/ijo.3.2.331
PMID:21573369
Abstract

Sixteen patients with squamous cell carcinoma of the head and neck region were studied for the formation of platinum-DNA adduct in leukocyte DNA. Every patient received carboplatin and cisplatin, each given intravenously on day 1 of 21-day treatment cycles. Blood was obtained for DNA isolation 24 hours after treatment on cycles 1 and 2; and on the morning before cycle 2 of therapy (21 days after cycle 1 drug delivery). Adduct was measured by atomic absorbance spectrometry with Zeeman background correction. As has been shown in previous studies, adduct persistence and accumulation could be demonstrated in a portion of the cohort. Adduct removal from blood cell DNA during the 21 days of cycle number 1, was determined for 12 patients. In these patients, adduct removal was directly i-elated to clinical resistance to the cisplatin/carboplatin treatment regimen; and adduct removal was inversely related to leukocyte toxicity. These data demonstrate that changes in adduct levels with time may provide valuable information, in the study of the human in vivo biology of platinum-DNA damage and repair.

摘要

对16例头颈部鳞状细胞癌患者的白细胞DNA中铂-DNA加合物的形成情况进行了研究。每位患者均接受卡铂和顺铂治疗,在21天的治疗周期的第1天静脉给药。在第1周期和第2周期治疗后24小时采集血样用于DNA分离;并在第2周期治疗前的早晨(第1周期给药后21天)采集血样。通过带有塞曼背景校正的原子吸收光谱法测量加合物。如先前研究所示,在部分队列中可证明加合物的持续存在和积累。对12例患者测定了第1周期21天期间血细胞DNA中加合物的清除情况。在这些患者中,加合物的清除与对顺铂/卡铂治疗方案的临床耐药性直接相关;加合物的清除与白细胞毒性呈负相关。这些数据表明,随着时间推移加合物水平的变化可能为研究铂-DNA损伤和修复的人体体内生物学提供有价值的信息。

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Cytotechnology. 1998 Sep;27(1-3):187-201. doi: 10.1023/A:1008016922425.