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

针对致癌物-DNA加合物的特异性抗体已经探测了 体外和体内DNA的性质、程度和后果 改性 生物样本替换为2- 乙酰氨基芴（AAF）、顺-二氨二氯铂II（顺- 苯并（a）芘（BP）的定量分析 免疫测定和免疫组织化学程序， 原位定位加合物。 在长期喂养的大鼠肝脏DNA中 致癌剂量的AAF，加合物去除具有双相性，表明 两个基因组区室-一个从中除去加合物 一种是快速的，另一种是缓慢的。 这些 动力学不是由于不同的肝细胞类型或DNA 与或多或少紧密结合的染色质区域相关 包括核基质 加合物和肿瘤剂量的比较 长期饲喂AAF的小鼠的膀胱和肝脏的反应显示， 线性加合物和肝肿瘤形成，但非线性膀胱 肿瘤形成 免疫组织化学定位2- AAF大鼠肝脏中AF-DNA加合物 证明了不均匀的加合物分布，并且在 几种不同的肝癌诱发的癌前病变， 创世协议 顺式-DDP-DNA加合物在来自 有核外周血细胞和几种组织中获得 在cis-DDP治疗过程中多次从癌症患者中 治疗和/或尸检。 加合物蓄积发生在 总累积剂量的函数。 疾病缓解数据55 卵巢癌患者和17例睾丸癌患者 加合物水平高的人有很高的 对治疗完全有反应 BP-DNA抗原性测定， 酶联免疫吸附测定（ELISA）43例血细胞DNA 消防员和40名控制人员。 在这两组中， 样本呈阳性，但平均加合物水平较高， 消防员的样本 其他促成因素 样本阳性是摄入木炭烧烤食物， smoking.

Antibodies specific for carcinogen-DNA adducts have probed the nature, extent, and consequences of in vitro and in vivo DNA modification. Biological samples substituted with 2- acetylaminofluorene (AAF), cis-diamminedichloroplatinum II (cis- DDP) and benzo(a)pyrene (BP) have been analyzed by quantitative immunoassays and by immunohistochemical procedures developed to localize adducts in situ. In hepatic DNA of rats chronically fed a carcinogenic dose of AAF, adduct removal has biphasic, suggesting two genomic compartments - one from which adducts are removed rapidly and another from which they are removed slowly. These kinetics are not due to different liver cell types or DNA associated with more or less tightly bound chromatin regions including the nuclear matrix. Comparison of adduct and tumor dose responses in bladder and liver of mice fed AAF chronically showed linear adduct and liver tumor formation, but non-linear bladder tumor formation. Immunohistochemical localization of 2- aminofluorene-DNA (AF-DNA) adducts in livers of rats fed AAF demonstrated a non-uniform adduct distribution and no adducts in preneoplastic foci induced by several different hepatocarcino- genesis protocols. Cis-DDP-DNA adducts were measured in DNA from nucleated peripheral blood cells and in several tissues obtained from cancer patients at multiple times during courses of cis-DDP therapy and/or at autopsy. Adduct accumulation occurred as a function of total cumulative dose. Disease response data on 55 ovarian cancer Patients and 17 testicular cancer patients indicated that individuals with high adduct levels have a high rate of complete response to therapy. BP-DNA antigenicity was measured in enzyme-linked immunosorbent assays (ELISA) blood cell DNA of 43 firefighters and 40 controls. In both groups about 30% of the samples were positive, but mean adduct levels were higher in samples from firefighters. Other factors which contributed to sample positivity were the ingestion of charcoal broiled foods and smoking.