Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane.
Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane.
复制标题
由氯氟烃取代2,2-二氯-1,1,1-三氟乙烷进行组织酰化。
DOI：
10.1073/pnas.88.4.1407
复制
发表时间：
1991
影响因子：
11.1
通讯作者：
Anders,MW
中科院分区：
文献类型：
--
作者：
Harris,JW;Pohl,LR;Martin,JL;Anders,MW
正在开发氢氯氟烃（HCFCs）作为消耗臭氧层的氯氟烃（CFCs）的替代品;由于预计人类可能会广泛接触HCFCs，因此必须彻底评估其毒性。在这里，我们报告的CFC替代2，2-二氯-1，1，1-三氟乙烷（HCFC-123）的生物活化的亲电中间体，与肝蛋白共价反应的研究。HCFC-123及其类似物氟烷（2-溴-2-氯-1，1，1-三氟乙烷）在大鼠中通过19 F NMR光谱进行了研究，我们发现三氟乙酰化赖氨酸加合物与肝蛋白形成。此外，与半抗原特异性抗三氟乙酰蛋白抗体免疫反应的蛋白质的模式是相同的HCFC-123和氟烷暴露大鼠的肝脏。由于氟烷引起特异质的，有时是致命的，肝炎，这是与免疫反应对几个三氟乙酰化的肝脏蛋白，目前的研究结果提出的可能性，即人类暴露于HCFC-123或结构相关的氟氯烃可能有发展免疫介导的肝炎的风险。
Hydrochlorofluorocarbons (HCFCs) are being developed as substitutes for ozone-depleting chlorofluorocarbons (CFCs); because widespread human exposure to HCFCs may be expected, it is important to evaluate their toxicities thoroughly. Here we report studies on the bioactivation of the CFC substitute 2,2-dichloro-1,1,1-trifluoroethane (HCFC-123) to an electrophilic intermediate that reacts covalently with liver proteins. HCFC-123 and its analog halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) were studied in rats by 19F NMR spectroscopy, and we found that a trifluoroacetylated lysine adduct was formed with liver proteins. Also, the pattern of proteins immunoreactive with hapten-specific anti-trifluoroacetylprotein antibodies was identical in livers of HCFC-123- and halothane-exposed rats. Because halothane causes an idiosyncratic, and sometimes fatal, hepatitis that is associated with an immune response against several trifluoroacetylated liver proteins, the present findings raise the possibility that humans exposed to HCFC-123 or structurally related HCFCs may be at risk of developing an immunologically mediated hepatitis.