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

致癌物-DNA加合物特异性抗体已用于定量 用顺铂替代的生物样品中的DNA修饰， 3 '-叠氮基-2'，3 '-双脱氧胸苷（AZT）和多环芳香 碳氢化合物（PAHs），通过定量免疫测定法和 免疫组化 之前观察到的高血压与高血压之间的相关性 卵巢癌患者血细胞DNA中顺铂-DNA加合物的形成水平 癌症患者和良好的临床反应正在 既往未经治疗的III期卵巢癌患者的血液样本 患者 因为铂类药物是用于卵巢癌患者的 在妊娠期间，顺铂-DNA加合物已被定位和加合 在妊娠患者的胎盘和胎儿组织中测量的持久性 暴露于顺铂的猴母体。 顺铂围产期暴露为 在大鼠和小鼠幼仔中生长至成年的致瘤性;并了解 所涉及的机制，DNA加合物在基因组和 大鼠母体和胎儿组织线粒体DNA。 母体组织 基因组DNA中的加合物水平高于胎儿组织，并且 线粒体DNA在脑和肝脏中的加合物比在肝脏中的多2- 40倍。 基因组DNA。 已获得顺铂-DNA加合物的剂量反应 在成年雄性小鼠睾丸、肝脏和肾脏中。 人乳腺癌 表皮生长因子（EGF）受体的细胞系显示 调节顺铂基因毒性。 顺铂-DNA加合物 在癌症患者的肿瘤、皮肤和血液中测定。 防艾 一种药物，AZT，已经被证明会产生与剂量相关的癌前事件 在给予AZT的动物中，小鼠阴道组织（肿瘤发生的靶点）中 在饮用水中28天。AZT被证明是 肝脏线粒体DNA。 优选AZT 靶向中国仓鼠卵巢细胞染色体的端粒区域。 美国 暴露于科威特油井大火的陆军人员遭受的多环芳烃较少 科威特不是德国。 抗血清正在被 对苯-蛋白质加合物诱发，并将用于监测 在中国和美国的苯接触工人。

Antibodies specific for carcinogen-DNA adducts have been used to quantify DNA modification in biological samples substituted with cisplatin, 3'-azido-2',3'-dideoxythymidine (AZT) and polycyclic aromatic hydrocarbons (PAHs) by quantitative immunoassays and immunohistochemistry. A previously-observed correlation between high levels of cisplatin-DNA adduct formation in 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. Because platinum drugs are given to ovarian cancer patients during pregnancy, cisplatin-DNA adducts have been localized and adduct persistence measured in placentas and fetal tissues from pregnant patas monkey dams exposed to cisplatin. Cisplatin perinatal exposure is tumorigenic in rat and mouse pups grown to adulthood; and to understand the mechanisms involved, DNA adducts were measured in genomic and mitochondrial DNA of rat maternal and fetal tissues. Maternal tissues had higher adduct levels than fetal tissues in genomic DNA, and mitochondrial DNA in brain and liver had 2- to 40-fold more adducts than genomic DNA. A dose-response for cisplatin-DNA adducts has been obtained in adult male mouse testis, liver and kidney. In human breast cancer cell lines the epidermal growth factor (EGF) receptor was shown to modulate cisplatin genotoxicity. Cisplatin-DNA adducts are being measured in tumor, skin and blood of cancer patients. The anti-AIDS drug, AZT, has been shown to produce dose-related preneoplastic events in mouse vaginal tissue (a target for tumorigenesis) in animals given AZT in the drinking water for 28 days. AZT was shown to incorporate into liver mitochondrial DNA in the same experiment. AZT preferentially targets telomeric regions of Chinese hamster ovary cell chromosomes. US Army personnel exposed to Kuwaiti oil well fires experienced less PAH exposure and DNA damage in Kuwait than in Germany. Antisera is being elicited against a benzene-protein adduct and will be used for monitoring benzene-exposed workers in China and in the United States.