Boogaard P J, Sumner S C, Turner M J, Bond J A
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Toxicology. 1996 Oct 28;113(1-3):297-9. doi: 10.1016/0300-483x(96)03460-9.
1,3-Butadiene (BD) is a carcinogen in rats and mice. Previous in vitro studies showed that mouse liver microsomes formed 1,2-epoxy-3-butene (BMO) from BD and 1,2:3,4-diepoxybutane (BDE) from BMO at much higher rates than rat or human microsomes. Blood and tissue levels of BDE were significantly lower in rats than in mice following exposure to BD. Since mice are much more susceptible to cancer induced by BD than rats, these findings suggest a key role for BDE in BD-induced carcinogenicity. The aim of this study was to characterize the glutathione (GSH) conjugation of BDE by cytosol from human liver and mouse and rat liver and lung in vitro. BDE and radiolabeled GSH were incubated with cytosol. Conjugates were identified by 13C-NMR and FAB mass spectroscopy and quantitated by HPLC. The enzyme kinetics for the conjugation of BDE with GSH suggest that the higher BDE blood concentrations in mice compared with rats following inhalation exposure to BD are not due to differences in GSH conjugation of BDE.
1,3 - 丁二烯（BD）对大鼠和小鼠具有致癌性。先前的体外研究表明，小鼠肝微粒体由BD生成1,2 - 环氧 - 3 - 丁烯（BMO）以及由BMO生成1,2:3,4 - 二环氧丁烷（BDE）的速率比大鼠或人类微粒体高得多。暴露于BD后，大鼠血液和组织中的BDE水平显著低于小鼠。由于小鼠比大鼠对BD诱导的癌症更敏感，这些发现表明BDE在BD诱导的致癌作用中起关键作用。本研究的目的是在体外表征人肝、小鼠肝和肺以及大鼠肝和肺的胞液对BDE的谷胱甘肽（GSH）结合作用。将BDE和放射性标记的GSH与胞液一起孵育。通过13C - NMR和FAB质谱鉴定结合物，并通过HPLC进行定量。BDE与GSH结合的酶动力学表明，吸入暴露于BD后，小鼠体内BDE的血液浓度高于大鼠，这并非由于BDE与GSH结合存在差异所致。
