Brady J F, Xiao F, Ning S M, Yang C S
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers University, Piscataway, NJ 08855.
Arch Toxicol. 1990;64(2):157-60. doi: 10.1007/BF01974403.
Exposure to methyl tertiary-butyl ether (MTBE), a commonly used octane booster in gasoline, has previously been shown to alter various muscle, kidney, and liver metabolic activities. In the present study, the metabolism of MTBE by liver microsomes from acetone- or phenobarbital-treated Sprague-Dawley rats was studied at concentrations of up to 5 mM MTBE. Equimolar amounts of tertiary-butanol, as measured by head-space gas chromatography, and formaldehyde were formed. The Vmax for the demethylation increased by 4-fold and 5.5-fold after acetone and phenobarbital treatments, respectively. The apparent Km value of 0.70 mM using control microsomes was decreased slightly after acetone treatment, but was increased by 2-fold after phenobarbital treatment. The metabolism of MTBE (1 mM) was inhibited by 35% by monoclonal antibodies against P450IIE1, the acetone/ethanol inducible form of cytochrome P450, suggesting a partial contribution by this isozyme. A single 18-h pretreatment of rats with 1 or 5 ml/kg MTBE (i.p.) resulted in a 50-fold induction of liver microsomal pentoxyresorufin dealkylase activity but no change in N-nitrosodimethylamine demethylase activity. These trends in activity agreed with immunoblot analysis which showed an elevation in P450IIB1 but no change in P450IIE1 levels.
甲基叔丁基醚（MTBE）是汽油中常用的辛烷值提升剂，此前已表明接触该物质会改变各种肌肉、肾脏和肝脏的代谢活动。在本研究中，研究了来自经丙酮或苯巴比妥处理的Sprague-Dawley大鼠的肝微粒体对MTBE的代谢情况，MTBE浓度高达5 mM。通过顶空气相色谱法测定，生成了等摩尔量的叔丁醇和甲醛。丙酮和苯巴比妥处理后，去甲基化的Vmax分别增加了4倍和5.5倍。使用对照微粒体时，表观Km值为0.70 mM，丙酮处理后略有下降，但苯巴比妥处理后增加了2倍。针对细胞色素P450的丙酮/乙醇诱导型P450IIE1的单克隆抗体抑制了MTBE（1 mM）35%的代谢，表明该同工酶有部分贡献。用1或5 ml/kg MTBE（腹腔注射）对大鼠进行单次18小时预处理，导致肝微粒体戊氧基试卤灵脱烷基酶活性诱导了50倍，但N-亚硝基二甲胺脱甲基酶活性没有变化。这些活性趋势与免疫印迹分析结果一致，免疫印迹分析显示P450IIB1升高，但P450IIE1水平没有变化。
