Kopjar Nevenka, Garaj-Vrhovac Vera, Milas Ivan
Laboratory of Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.
Teratog Carcinog Mutagen. 2002;22(1):13-30. doi: 10.1002/tcm.1035.
The alkaline comet assay was employed to assess the pre- and post-treatment levels of in vivo DNA damage in peripheral blood leukocytes of cancer patients. During the study all patients were given antineoplastic drugs, mainly as polychemotherapy. To quantify the DNA damage, two different comet parameters were evaluated: the tail length and the tail moment. Our results indicate marked interindividual variations between baseline DNA damage in peripheral blood leukocytes recorded among cancer patients prior to the chemotherapy. After intravenous administration of various antineoplastic drugs, a significantly increased level of DNA damage in all cancer patients compared to their pre-treatment values was recorded The highest level of DNA damage was seen following administration of 5-fluorouracil, adriamycin, and cisplatin (FAP protocol). The results indicate that administration of antineoplastic drugs in standard protocols is accompanied by significant DNA damage in peripheral blood leukocytes. In order to diminish the potential risks of developing second neoplasms, a continuous biomonitoring of cancer patients after the ending of chemotherapy becomes important. Despite their limitations, present results confirm the usefulness of the alkaline comet assay as a sensitive biomarker of exposure that enables rapid and simple detection of primary DNA damage in peripheral blood leukocytes of cancer patients. Together with standard cytogenetic endpoints, the comet assay provides a powerful technique for the routine detection of critical DNA lesions produced after administration of antineoplastic drugs in the clinical settings.
采用碱性彗星试验评估癌症患者外周血白细胞体内DNA损伤的治疗前和治疗后水平。在研究期间,所有患者均接受抗肿瘤药物治疗,主要是联合化疗。为了量化DNA损伤,评估了两个不同的彗星参数:尾长和尾矩。我们的结果表明,化疗前癌症患者外周血白细胞基线DNA损伤存在明显的个体差异。静脉注射各种抗肿瘤药物后,记录到所有癌症患者的DNA损伤水平与治疗前相比显著增加。在使用5-氟尿嘧啶、阿霉素和顺铂(FAP方案)后,DNA损伤水平最高。结果表明,按照标准方案使用抗肿瘤药物会导致外周血白细胞出现明显的DNA损伤。为了降低发生第二肿瘤的潜在风险,化疗结束后对癌症患者进行持续的生物监测变得很重要。尽管存在局限性,但目前的结果证实了碱性彗星试验作为一种敏感的暴露生物标志物的有用性,它能够快速、简单地检测癌症患者外周血白细胞中的原发性DNA损伤。与标准细胞遗传学终点一起,彗星试验为临床环境中使用抗肿瘤药物后产生的关键DNA损伤的常规检测提供了一种强大的技术。