Himmelstein M W, Turner M J, Asgharian B, Bond J A
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Toxicology. 1996 Oct 28;113(1-3):306-9. doi: 10.1016/0300-483x(96)03462-2.
Significant species differences exist in the susceptibility to butadiene (BD)-induced cancer in rats and mice, and metabolism is likely a critical determinant for species sensitivity. This study measured the in vivo concentrations of, (1) BD in blood; (2) epoxybutene (EB) and diepoxybutane (DEB) in blood, lung and liver; and (3) glutathione (GSH) in lung and liver of male B6C3F1 mice and Sprague-Dawley rats during and after 6-h exposure to 62.5, 625, 1250, and 8000 (rat only) ppm BD. Mice had higher concentrations of EB and DEB in blood and tissues than did rats, DEB could not be detected in blood or tissues of rats, and the greatest depletion of GSH occurred in the lungs of mice. During exposure, the peak concentrations of EB in mice compared with rats were 4- to 8-fold higher in blood, 13- to 15-fold higher in lung, and 5- to 8-fold higher in liver. These data suggest that higher levels of BD epoxides in blood and tissues of mice compared with rats may explain, in part, the greater sensitivity of mice than rats to BD-induced carcinogenicity.
大鼠和小鼠对丁二烯（BD）诱导的癌症易感性存在显著的物种差异，代谢可能是物种敏感性的关键决定因素。本研究测定了雄性B6C3F1小鼠和Sprague-Dawley大鼠在暴露于62.5、625、1250和8000（仅针对大鼠）ppm BD 6小时期间及之后，（1）血液中的BD；（2）血液、肺和肝脏中的环氧丁烯（EB）和1,2-二环氧丁烷（DEB）；以及（3）肺和肝脏中的谷胱甘肽（GSH）的体内浓度。小鼠血液和组织中的EB和DEB浓度高于大鼠，在大鼠的血液或组织中未检测到DEB，并且GSH的最大消耗发生在小鼠的肺部。在暴露期间，与大鼠相比，小鼠血液中EB的峰值浓度高4至8倍，肺中高13至15倍，肝脏中高5至8倍。这些数据表明，与大鼠相比，小鼠血液和组织中BD环氧化物水平较高可能部分解释了小鼠比大鼠对BD诱导的致癌性更敏感的原因。
