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.

用单克隆研究研究了细胞色素P-450的多样性 抗3-甲基胆碱（MC）诱导的大鼠肝细胞色素的抗体（mAb） P-450。 半定量的直接放射免疫测定（RIA）是 开发以测量来自各种微粒体中的细胞色素P-450 未经治疗或用MC处理的动物中的组织。 金额 不同组织和物种中的细胞色素P-450，包括人类样品 通过竞争性RIA检查了胎盘和淋巴细胞。 通过这种方法观察到个体差异，这更多 比酶活性的测量可靠。 女性的胎盘 烟熏香烟含有更多的细胞色素P-450 比非吸烟者的胎盘特异性表位。 数量 在人外周淋巴细胞中的mAb特异性细胞色素P-450增加 用苯子（A）蒽治疗后。 带有多个mab的rias也有 用于检测动物肝脏中表位特异性细胞色素P-450， 目的是将各种组织分类有关MAB特异性 细胞色素P-450。 识别的细胞色素P-450水平要高得多 在MC处理的大鼠和C57BL/6小鼠中观察到MAB 1-7-1，而不是在 未经治疗的大鼠，经过MC治疗的DBA/2小鼠和豚鼠。 这些分析 提供一种研究细胞色素P-450多重性的方法 酶和结构研究的补充。 RIA方法将有助于 在不同的不同 组织，物种和实验动物的菌株，以及理解 细胞色素P-450的多样性及其在个体中的作用 对癌变的敏感性。