Kline S A, Robertson J F, Grotz V L, Goldstein B D, Witz G
Department of Environmental and Community Medicine, University of Medicine and Dentistry-New Jersey, Robert Wood Johnson Medical School, Piscataway.
Environ Health Perspect. 1993 Sep;101(4):310-2. doi: 10.1289/ehp.93101310.
We studied the in vivo metabolism of benzene in mice to ring-opened compounds excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene (110-440 mg/kg), [14C]benzene (220 mg/kg) or trans, trans-muconaldehyde (MUC; 4 mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24 hr, was extracted and analyzed by HPLC with a diode-array detector and by scintillation counting. In addition to trans,trans-muconic acid, previously the only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy-trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with either benzene or MUC. We identified the new metabolite based on coelution of metabolites and UV spectral comparison with authentic standards in unmethylated and methylated urine extracts. Results presented here are consistent with the intermediacy of MUC in the in vivo metabolism of benzene to ring-opened metabolites.
我们研究了小鼠体内苯向尿液中排泄的开环化合物的代谢情况。雄性CD-1小鼠腹腔注射苯（110 - 440毫克/千克）、[14C]苯（220毫克/千克）或反式，反式-粘糠醛（MUC；4毫克/千克，苯的一种微粒体、血液毒性代谢产物）。收集24小时内的尿液，进行提取，并通过配备二极管阵列检测器的高效液相色谱法和闪烁计数法进行分析。除了反式，反式-粘糠酸（之前唯一已知的尿液中苯的开环代谢产物）外，在用苯或MUC处理的小鼠尿液中还检测到一种新的代谢产物，即6-羟基-反式，反式-2,4-己二烯酸。我们通过代谢产物的共洗脱以及与未甲基化和甲基化尿液提取物中真实标准品的紫外光谱比较来鉴定这种新的代谢产物。此处呈现的结果与MUC在苯向开环代谢产物的体内代谢过程中作为中间产物的情况一致。
