Day B W, Naylor S, Gan L S, Sahali Y, Nguyen T T, Skipper P L, Wishnok J S, Tannenbaum S R
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139.
Cancer Res. 1990 Aug 1;50(15):4611-8.
Ten reactive metabolites of five polycyclic aromatic hydrocarbons and styrene were investigated to determine the generality of ester adduct formation with human hemoglobin in the form of RBC and hydrolysis to the corresponding tetrahydrotetrols or dihydrodiols. No exceptions were noted among the compounds tested, which included the anti-diol epoxides of benzo[a]pyrene (BaP), chrysene, and benz[a]anthracene; the syn-diol epoxide of BaP; a mixture of syn- and anti-diol epoxides of benzo[e]pyrene; and epoxides of styrene, benzo[e]pyrene, BaP, and cyclopenta[c,d]pyrene. A test of the propensity of the simplest benzylic epoxide, styrene oxide, to form esters that hydrolyze via a BAL1 mechanism was performed. Hydrolysis of styrene oxide-adducted hemoglobin in H2(18)O at neutral pH yielded 18O incorporation results that suggest this mechanism of hydrolysis is operant to a minor degree in styrene oxide-hemoglobin ester adducts. A method was developed for the isolation and quantification of the polycyclic aromatic alcohols, which consists of enzymatic proteolysis, immunoaffinity chromatography, and gas chromatography-mass spectrometry or fluorimetry. The method allows for routine analysis of hemoglobin from individual samples as small as 1 ml of whole blood. Analysis of blood from different human populations revealed that hemoglobin adducts of the anti-diol epoxide of BaP dominated the spectrum of adducts formed by the selected metabolites.
研究了五种多环芳烃和苯乙烯的十种反应性代谢物，以确定其与红细胞形式的人血红蛋白形成酯加合物并水解为相应的四氢四醇或二氢二醇的普遍性。在所测试的化合物中未发现例外情况，这些化合物包括苯并[a]芘（BaP）、 Chrysene和苯并[a]蒽的反式二醇环氧化物；BaP的顺式二醇环氧化物；苯并[e]芘的顺式和反式二醇环氧化物混合物；以及苯乙烯、苯并[e]芘、BaP和环戊[c,d]芘的环氧化物。对最简单的苄基环氧化物氧化苯乙烯形成通过BAL1机制水解的酯的倾向进行了测试。在中性pH下，在H2(18)O中氧化苯乙烯加合的血红蛋白的水解产生了18O掺入结果，表明这种水解机制在氧化苯乙烯-血红蛋白酯加合物中仅在较小程度上起作用。开发了一种分离和定量多环芳烃醇的方法，该方法包括酶促蛋白水解、免疫亲和色谱和气相色谱-质谱或荧光测定法。该方法允许对小至1毫升全血的个体样本中的血红蛋白进行常规分析。对不同人群血液的分析表明，BaP反式二醇环氧化物的血红蛋白加合物在所选代谢物形成的加合物谱中占主导地位。
