Bailey E, Brooks A G, Bird I, Farmer P B, Street B
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, United Kingdom.
Anal Biochem. 1990 Nov 1;190(2):175-81. doi: 10.1016/0003-2697(90)90177-b.
The determination of the covalently bound reaction products of 4,4'-methylenedianiline (MDA) to hemoglobin was investigated as a possible method for biological dosimetry in humans. The extent of binding to rat hemoglobin of MDA was determined by dosing animals with the 14C-ring-labeled compound. Two adducts were released from the hemoglobin on hydrolysis under mildly basic conditions which were identified as MDA and N-acetyl-MDA and accounted for between 36 and 45% of the total radioactivity bound to the protein. A quantitative assay procedure was subsequently developed for measuring both of the base released adducts in rat hemoglobin. The method utilized solvent extraction followed by derivatization with pentafluoropropionic anhydride and subsequent separation and quantitation by capillary gas chromatography with selective ion monitoring mass spectrometry using deuterium-labeled analogues of MDA and N-acetyl-MDA as internal standards. A dose-response relationship was established in orally dosed rats between production of each of the hemoglobin released adducts and dose of MDA (1-12 mg/kg). The possible use of such adduct determinations as dosimeters for industrial workers exposed to MDA is discussed.
对4,4'-亚甲基二苯胺（MDA）与血红蛋白的共价结合反应产物进行测定，作为一种可能用于人体生物剂量测定的方法进行了研究。通过给动物投喂14C环标记化合物来确定MDA与大鼠血红蛋白的结合程度。在温和碱性条件下水解时，从血红蛋白中释放出两种加合物，鉴定为MDA和N-乙酰-MDA，它们占与蛋白质结合的总放射性的36%至45%。随后开发了一种定量分析程序，用于测量大鼠血红蛋白中释放的两种碱基加合物。该方法采用溶剂萃取，然后用五氟丙酸酐衍生化，随后通过毛细管气相色谱结合选择性离子监测质谱进行分离和定量，使用氘标记的MDA和N-乙酰-MDA类似物作为内标。在口服给药的大鼠中，建立了每种血红蛋白释放加合物的产生与MDA剂量（1-12 mg/kg）之间的剂量反应关系。讨论了将这种加合物测定用作接触MDA的产业工人剂量计的可能性。
