RADIOIMMUNOASSAY OF CYTOCHROMES P-450 USING MONOCLONAL ANTIBODIES

使用单克隆抗体对细胞色素 P-450 进行放射免疫测定

• 批准号: 4692384
• 负责人: B J SONG
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692384
• 关键词: chemical carcinogenesis; cytochrome P450; genetic strain; hemoprotein structure; human tissue; methylcholanthrene; microsomes; monoclonal antibody; phenobarbital; radioimmunoassay; species difference; tissues

The multiplicity of cytochromes P-450 is being studied with monoclonal antibodies (MAbs) to 3-methylcholanthrene (MC)-induced rat liver cytochrome P-450. A semiquantitative, direct radioimmunoassay (RIA) has been developed to measure cytochrome P-450 in the microsomes from various tissues in animals that are untreated, or treated with MC. The amounts of cytochrome P-450 in different tissues and species, including human samples such as placentas and lymphocytes, were examined by competitive RIA. Individual differences have been observed by this method, which is more reliable than measurements of enzyme activity. Placentas from women who smoked cigarettes contained greater amounts of cytochrome P-450 with the MAb-specific epitope than placentas from nonsmokers. The amount of MAb-specific cytochrome P-450 in human peripheral lymphocytes increased after treatment with benz(a)anthracene. RIAs with multiple MAbs have also been used to detect epitope-specific cytochromes P-450 in animal livers, with the goal of classifying various tissues with respect to MAb-specific cytochromes P-450. Much higher levels of cytochrome P-450 recognized by MAb 1-7-1 were observed in MC-treated rats and C57BL/6 mice than in untreated rats, MC-treated DBA/2 mice and guinea pigs. These analyses provide an approach to the study of cytochrome P-450 multiplicity that is complementary to enzymatic and structural studies. RIA methods will aid in defining the epitope-specific cytochromes P-450 content in different tissues, species, and strains of laboratory animals, and in understanding the diversity of the cytochromes P-450 and their role in individual susceptibility to carcinogenesis.

细胞色素P-450的多样性正在用单克隆抗体进行研究。 抗3-甲基胆蒽（MC）诱导的大鼠肝细胞色素 P-450 半定量、直接放射免疫测定（RIA）已被 开发用于测量来自各种微粒体中的细胞色素P-450 未处理或用MC处理的动物中的组织。 的量 不同组织和物种中的细胞色素P-450，包括人体样本 如胎盘和淋巴细胞。 通过这种方法观察到了个体差异， 比测量酶活性更可靠。 胎盘来自那些 吸烟的香烟含有更大量的细胞色素P-450， MAb特异性表位比非吸烟者的胎盘。 的量 人外周血淋巴细胞中MAb特异性细胞色素P-450增加 在用苯并（a）蒽处理之后。 具有多个MAb的RIA还 用于检测动物肝脏中表位特异性细胞色素P-450， 目的是根据MAb特异性 细胞色素P-450。 细胞色素P-450水平高得多， 在MC处理的大鼠和C57 BL/6小鼠中观察到MAb 1-7-1，而在MC处理的大鼠和C57 BL/6小鼠中观察到MAb 1-7-1。 未处理的大鼠、MC处理的DBA/2小鼠和豚鼠。 这些分析 提供了一种研究细胞色素P-450多样性的方法， 补充酶和结构研究。 RIA方法将有助于 确定不同细胞中表位特异性细胞色素P-450含量， 实验动物的组织、种属和品系， 细胞色素P-450的多样性及其在个体中的作用 对致癌作用的敏感性。