Forkert P G, Vessey M L, Elce J S, Park S S, Gelboin H V, Cole S P
Res Commun Chem Pathol Pharmacol. 1986 Aug;53(2):147-57.
The cytochromes P-450 are key components of the mixed-function oxidase system responsible for the biotransformation of many foreign compounds to mutagens and carcinogens. In the present study, the distribution of these hemoproteins in frozen sections of mouse lung was determined immunohistochemically, using monoclonal antibodies (Mabs). Mab 1-7-1 is specific for 3-methylcholanthrene-inducible cytochromes P-450; this Mab reacted intensely with parenchymal cells, but not epithelial cells of pulmonary bronchioles of 3-methylcholanthrene-treated mice. Mab 1-7-1 did not react with pulmonary cells of either untreated or phenobarbital-treated mice. Mab specific for phenobarbital-inducible cytochromes P-450, Mab 2-66-3, reacted with parenchymal and bronchiolar epithelial cells in the lungs of phenobarbital-treated, 3-methylcholanthrene-treated, and untreated mice. The localization of constitutive and induced forms of cytochrome P-450 in different cells of the lung may provide insight into the mechanisms by which cell-specific damage and carcinogenicity are evoked by xenobiotics.
细胞色素P-450是混合功能氧化酶系统的关键组成部分,负责将许多外来化合物生物转化为诱变剂和致癌物。在本研究中,使用单克隆抗体(Mab)通过免疫组织化学方法确定了这些血红蛋白在小鼠肺冷冻切片中的分布。Mab 1-7-1对3-甲基胆蒽诱导的细胞色素P-450具有特异性;这种单克隆抗体与实质细胞强烈反应,但与3-甲基胆蒽处理小鼠的肺细支气管上皮细胞不反应。Mab 1-7-1与未处理或苯巴比妥处理小鼠的肺细胞均无反应。对苯巴比妥诱导的细胞色素P-450具有特异性的单克隆抗体Mab 2-66-3,与苯巴比妥处理、3-甲基胆蒽处理和未处理小鼠肺中的实质细胞和细支气管上皮细胞反应。细胞色素P-450的组成型和诱导型在肺不同细胞中的定位可能有助于深入了解外源性物质引起细胞特异性损伤和致癌性的机制。