Kaufman D G
Environ Health Perspect. 1976 Aug;16:99-110. doi: 10.1289/ehp.761699.
The epithelial lining of respiratory air passageways is a primary target tissue for toxicity and carcinogenesis in man and in animal models of human disease. The importance of this target tissue was the basis for development of methods to study its biochemistry, and with this information to distinguish the unique properties of this tissue from properties common to all cell types. Biochemical methods employed labeling of macromolecules in isolated hamster treacheas during brief (less than 4 hr) incubation in vitro. Studies of RNA metabolism in isolated tracheas demonstrated a pattern of maturation of ribosomal RNA like that shown for other cell types. Alterations in RNA metabolism were observed in isolated tracheas obtained from vitamin A-deficient hamsters and hamsters previously treated by intratracheal administration of benzo[a]pyrene (BP) plus ferric oxide (Fe2O3) in vivo. Studies with toyocamycin, actinomycin D, and alpha-amanitin, all inhibitors of RNA metabolism, were performed to characterize the class of RNA molecules with a decreased proportion of labeling in tracheas from vitamin A deficient hamsters. In another series of experiments, BP was shown to bind to DNA in epithelial cells of isolated tracheas. The quantity of BP binding was increased by prior intratracheal treatment of hamsters with BP plus Fe2O3 in vivo, this induced binding was inhibited by addition of 7,8-benzoflavone to the incubation medium. Increased BP binding was also observed in isolated tracheas from hamsters believed to be in states of increased susceptibility to respiratory carcinogenesis in vivo. The results show that biochemical studies are feasible with this tissue. Furthermore, a number of questions of importance with regard to this target epithelium are best studied directly in its constituent cells.
呼吸道的上皮衬里是人类和人类疾病动物模型中毒性和致癌作用的主要靶组织。这个靶组织的重要性是开发研究其生物化学方法的基础，并利用这些信息将该组织的独特特性与所有细胞类型共有的特性区分开来。生化方法采用在体外短暂（少于4小时）孵育期间对分离的仓鼠气管中的大分子进行标记。对分离气管中RNA代谢的研究表明，核糖体RNA的成熟模式与其他细胞类型所示的模式相似。在从维生素A缺乏的仓鼠和先前在体内经气管内给予苯并[a]芘（BP）加三氧化二铁（Fe2O3）处理的仓鼠获得的分离气管中观察到RNA代谢的改变。使用RNA代谢的所有抑制剂丰加霉素、放线菌素D和α-鹅膏蕈碱进行研究，以表征在维生素A缺乏仓鼠的气管中标记比例降低的RNA分子类别。在另一系列实验中，BP被证明与分离气管的上皮细胞中的DNA结合。体内用BP加Fe2O3对仓鼠进行气管内预处理可增加BP的结合量，向孵育培养基中添加7,8-苯并黄酮可抑制这种诱导的结合。在被认为在体内对呼吸道致癌易感性增加的仓鼠的分离气管中也观察到BP结合增加。结果表明，对该组织进行生化研究是可行的。此外，关于这个靶上皮的许多重要问题最好直接在其组成细胞中进行研究。
