Poirier M C, Egorin M J, Fichtinger-Schepman A M, Yuspa S H, Reed E
National Cancer Institute, Bethesda, MD.
IARC Sci Publ. 1988(89):313-20.
An enzyme-linked immunosorbent assay (ELISA) has been developed with an antiserum elicited against cisplatin-modified DNA and used to quantify the intrastrand bidentate d(GpG)- and d(ApG)-diammineplatinum adducts in DNA samples prepared from nucleated blood cells and tissues of cancer patients receiving cisplatin or carboplatin chemotherapy. In nucleated blood cell DNA, adducts accumulated with increasing dose administered over a period of months, and a correlation was observed between the ability of a patient to form high levels of adduct and the frequency of tumour remission. Thus, many patients who did not form adducts also did not respond to therapy. Adduct distribution was shown to be widespread in many human tissues, and similar quantities of adducts were formed in peripheral blood cell DNA and tumour tissue. In addition, evidence suggests that residues of persistent adducts remain in many tissues weeks and even months after treatment. All of the above observations were obtained with the cisplatin-DNA ELISA; however, in comparison with other published data, the adduct levels reported are low. It now appears certain that the cisplatin-DNA ELISA results in an underestimation of adduct values in biological samples, since some human samples have been assayed by both this and two other procedures--the G-Pt-GMP ELISA and atomic absorbance spectroscopy. Values obtained with the two other procedures compare well with each other, but those obtained with the cisplatin-DNA ELISA for three human samples are 10-300-fold lower. The factors that result in this discrepancy are still under investigation.
已开发出一种酶联免疫吸附测定法（ELISA），该方法使用针对顺铂修饰DNA产生的抗血清，用于定量从接受顺铂或卡铂化疗的癌症患者的有核血细胞和组织中制备的DNA样本中的链内双齿d（GpG）-和d（ApG）-二胺铂加合物。在有核血细胞DNA中，加合物在数月内随着给药剂量的增加而积累，并且观察到患者形成高水平加合物的能力与肿瘤缓解频率之间存在相关性。因此，许多未形成加合物的患者对治疗也无反应。加合物分布显示在许多人体组织中广泛存在，并且在外周血细胞DNA和肿瘤组织中形成的加合物数量相似。此外，有证据表明，在治疗后数周甚至数月，许多组织中仍残留有持久性加合物。上述所有观察结果均通过顺铂-DNA ELISA获得；然而，与其他已发表的数据相比，所报告的加合物水平较低。现在可以确定的是，顺铂-DNA ELISA导致对生物样品中加合物值的低估，因为一些人类样品已通过这种方法以及另外两种方法——G-Pt-GMP ELISA和原子吸收光谱法进行了检测。用另外两种方法获得的值彼此比较吻合，但用顺铂-DNA ELISA对三个人类样品获得的值要低10-300倍。导致这种差异的因素仍在研究中。
