Albrecht W, Neumann H G
Arch Toxicol. 1985 Apr;57(1):1-5. doi: 10.1007/BF00286566.
Covalent binding to hemoglobin was studied to further substantiate the proposal that it may be used for biomonitoring N-substituted aryl compounds. (14C)-Labeled acetanilide and nitrobenzene were orally administered to female Wistar rats and binding indices [Binding(mmol/mol Hb)/Dose(mmol/kg)] determined; these were 12 +/- 1 and 73 +/- 10, respectively. After mild acidic or alkaline hydrolysis, 90% of the bound material was released and identified as aniline by radio thin layer chromatography. This supports the hypothesis that nitroso aryl derivatives, common intermediates in the metabolism of N-substituted aryl compounds, react with SH-groups of hemoglobin to yield sulfinic acid amides. Aniline was furthermore identified and quantified by capillary gas chromatography, using hemoglobin from animals treated with unlabeled aniline and nitrobenzene. Binding indices in this case were 30 +/- 3 and 85 +/- 19, respectively. With this method human blood samples may also be analysed. Although nitrobenzene is known to produce less methemoglobin than aniline, hemoglobin binding is higher. This indicates that hemoglobin binding may be a better index of body burden than methemoglobin levels in biomonitoring N-substituted aryl compounds.
研究了与血红蛋白的共价结合，以进一步证实其可用于生物监测N-取代芳基化合物的提议。将（14C）标记的乙酰苯胺和硝基苯经口给予雌性Wistar大鼠，并测定结合指数[结合量（mmol/mol血红蛋白）/剂量（mmol/kg）]；分别为12±1和73±10。经过轻度酸性或碱性水解后，90%的结合物被释放，并通过放射性薄层色谱法鉴定为苯胺。这支持了以下假设：亚硝基芳基衍生物是N-取代芳基化合物代谢中的常见中间体，它与血红蛋白的SH基团反应生成亚磺酸酰胺。此外，使用未标记苯胺和硝基苯处理的动物的血红蛋白，通过毛细管气相色谱法对苯胺进行了鉴定和定量。在这种情况下，结合指数分别为30±3和85±19。用这种方法也可以分析人体血液样本。虽然已知硝基苯产生的高铁血红蛋白比苯胺少，但血红蛋白结合率更高。这表明在生物监测N-取代芳基化合物时，血红蛋白结合可能比高铁血红蛋白水平更能反映体内负荷。
