USE OF IMMUNOLOGICAL TECHNIQUES TO STUDY THE INTERACTION OF CARCINOGENS WITH DNA

针对致癌物-DNA加合物的抗体已被用于量化 多环取代生物样品中的DNA修饰 芳香烃(PAH)。顺铂和3‘-叠氮-2’.3‘- 双脱氧胸腺嘧啶核苷(AZT)的定量免疫测定和 免疫组织化学。测量多环芳烃-DNA加合物的研究 暴露在科威特油井大火中的陆军人员的血细胞DNA。 利用苯并[a]芘-DNA解离增强型稀土元素 荧光免疫分析(DELFIA)和32P标记后标记。显示出减少了 与随后在德国度过的时间相比，在科威特的DNA加合物。 这与科威特在该地区观察到的更清洁的空气有关。 士兵的工作地点。之前观察到的关联 在有核血液中高水平顺铂-DNA加合物形成之间 卵巢癌患者的细胞DNA和临床反应良好 在之前未经治疗的III期血液样本中得到验证 卵巢癌患者接受西南肿瘤组9249方案治疗。 与疾病反应相关的其他参数包括HPRT 诱变作用与铂类药物的药代动力学。因为铂类药物 是在怀孕期间给卵巢癌患者服用的。顺铂-DNA 加合物被本地化并在胎盘中测量加合物持久性 以及暴露于顺铂的妊娠帕塔斯猴的胎儿组织。 此外。围产期铂类药物暴露可致大鼠肿瘤 小老鼠。DNA加合物在幼崽身上进行了测量， 致癌的顺铂暴露。抗艾滋病药物。AZT。已经展示了 产生与剂量相关的癌前事件，包括药物DNA 掺入、上皮细胞增殖和α6-整合素染色 在小鼠阴道组织(肿瘤发生的靶点)中 动物在饮水中给予AZT 28天。AZT掺入 对肝脏基因组和线粒体DNA的研究正在进行中。这种药有 免疫组织化学和定量检测均显示 优先靶向CHO细胞染色体的端粒区域。抗血清 是由一种苯蛋白加合物引起的，但高滴度的血清 还没有得到。将使用抗血清进行监测 中国和美国接触苯的工人的数量。

Antibodies specific for carcinogen-DNA adducts have been used to quantify DNA modification in biological samples substituted with polycyclic aromatic hydrocarbons (PAH). cisplatin and 3' -azido-2' .3' - dideoxythymidine (AZT) by quantitative immunoassays and immunohistochemistry. Studies conducted to measure PAH-DNA adducts in blood cell DNA of Army personnel exposed to oil well fires in Kuwait. using the benzo[a]pyrene-DNA dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) and 32P-postlabeling. showed a reduction of DNA adducts in Kuwait as compared to subsequent time spent in Germany. This correlated with observations of cleaner air in Kuwait in the area of the soldiers' duty stations. A previously-observed correlation between high levels of cisplatin-DNA adduct formation in nucleated blood cell DNA of ovarian cancer patients and favorable clinical responses is being validated in blood samples from previously-untreated Stage III ovarian cancer patients on the Southwest Oncology Group 9249 protocol. Other parameters to be correlated with disease response are HPRT mutagenesis and platinum drug pharmacokinetics. Because platinum drugs are given to ovarian cancer patients during pregnancy. cisplatin-DNA adducts are being localized and adduct persistence measured in placentas and fetal tissues from pregnant patas monkey dams exposed to cisplatin. In addition. perinatal platinum drug exposure is tumorigenic in rat and mouse pups. and DNA adducts are being measured in the pups after tumorigenic cisplatin exposures. The anti-AIDS drug. AZT. has been shown to produce dose-related preneoplastic events, including drug-DNA incorporation, epithelial proliferation and alpha6-integrin staining expansion, in mouse vaginal tissue (a target for tumorigenesis) in animals given AZT in the drinking water for 28 days. AZT incorporation into liver genomic and mitochondrial DNA is under study. This drug has been shown both immunohistochemically and quantitatively to preferentially target telomeric regions of CHO cell chromosomes. Antisera is being elicited against a benzene-protein adduct, but high-titer serum has not been obtained yet. The anti serum will be used for the monitoring of benzene-exposed workers in China and in the United States.