McDiarmid M A, Iype P T, Kolodner K, Jacobson-Kram D, Strickland P T
Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205.
Mutat Res. 1991 May;248(1):93-9. doi: 10.1016/0027-5107(91)90091-2.
Monitoring human populations for specific DNA modifications has been made possible by developing highly sensitive immunoassays employing antibodies specific for carcinogen-DNA adducts. While these techniques have been used to follow occupationally and environmentally exposed populations, results have been limited by the lack of exposure data with which to correlate adduct formation. Cancer patients treated with precisely known doses of anticancer drugs can be studied to examine the association between drug dose and adduct formation. This study examined acrolein-modified DNA in patients treated with the anticancer drug cyclophosphamide (CP) and in newly diagnosed patients prior to treatment. Employing 2 different detection methods, enzyme-linked immunosorbent assay (ELISA) and immuno-dot blot (IDB), acrolein-modified DNA was identified in a total of 6 of 12 (50%) treated patients and in 0 of 15 untreated patients. Formation of acrolein-modified DNA was examined as a function of lifetime CP dose, recent CP dose, time since last treatment, regime of treatment, and smoking history; however no clear trends were observed.
通过开发高度灵敏的免疫测定法，利用针对致癌物-DNA加合物的特异性抗体，实现了对特定DNA修饰的人群监测。虽然这些技术已用于跟踪职业和环境暴露人群，但结果受到缺乏与加合物形成相关的暴露数据的限制。可以对接受精确已知剂量抗癌药物治疗的癌症患者进行研究，以检查药物剂量与加合物形成之间的关联。本研究检查了接受抗癌药物环磷酰胺（CP）治疗的患者以及新诊断未治疗患者中的丙烯醛修饰DNA。采用两种不同的检测方法，即酶联免疫吸附测定（ELISA）和免疫斑点印迹（IDB），在12名接受治疗的患者中有6名（50%）检测到丙烯醛修饰DNA，而15名未治疗患者中未检测到。研究了丙烯醛修饰DNA的形成与终身CP剂量、近期CP剂量、上次治疗后的时间、治疗方案和吸烟史的关系；然而，未观察到明显趋势。
