Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol:: a potential biomarker for toluene exposure
Formation of DNA adducts in HL-60 cells treated with the toluene metabolite p-cresol:: a potential biomarker for toluene exposure
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DOI：
10.1016/s0009-2797(02)00249-1
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发表时间：
2003-05-06
影响因子：
5.1
通讯作者：
Bodell, WJ
中科院分区：
文献类型：
--
作者：
Gaikwad, NW;Bodell, WJ
我们检查了用甲苯代谢物对甲酚处理的含有髓过氧化物酶的 HL-60 细胞中 DNA 加合物的形成。用对甲酚和 H2O2 组合处理 HL-60 细胞产生四种 DNA 加合物 1: (75.0%)、2: (9.1%)、3: (7.0%) 和 4: (8.8%)，加合物水平范围为 0.3 至 33.6 x 10(-7)。对甲酚形成的 DNA 加合物的水平取决于对甲酚、H2O2 的浓度和处理时间。对甲酚与髓过氧化物酶和 H2O2 的体外孵育产生三种 DNA 加合物 1: (40.5%)、2: (28.4%) 和 3: (29.7%)，相对加合物水平为 0.7 x 10(-7)。通过 Ag(1)O 氧化制备对甲酚醌甲基化物衍生物 (PCQM)。小牛胸腺DNA与PCQM的反应产生四种加合物1: (18.5%)、2: (36.4%)、3: (29.0%)和5: (16.0%)，相对加合物水平为1.6 x 10(-7)。重色谱分析表明，用对甲酚处理的 HL-60 细胞中以及髓过氧化物酶激活对甲酚后形成的 DNA 加合物 1-3 与 DNA 与 PCQM 反应形成的相似。这一观察结果表明，在这些活化系统中，对甲酚被活化为醌甲基化物中间体。总而言之，这些结果表明 PCQM 是导致用对甲酚处理的 HL-60 细胞中形成 DNA 加合物的反应中间体。此外，PCQM 形成的 DNA 加合物可以提供生物标志物来评估职业接触甲苯的情况。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
We have examined DNA adduct formation in myeloperoxidase containing HL-60 cells treated with the toluene metabolite p-cresol. Treatment of HL-60 cells with the combination of p- cresol and H2O2 produced four DNA adducts 1: (75.0%), 2: (9.1%), 3: (7.0%) and 4: (8.8%) and adduct levels ranging from 0.3 to 33.6 x 10(-7). The levels of DNA adducts formed by p-cresol were dependent on concentrations of p-cresol, H2O2 and treatment time. In vitro incubation of p-cresol with myeloperoxidase and H2O2 produced three DNA adducts 1: (40.5%), 2: (28.4%) and 3: (29.7%) with a relative adduct level of 0.7 x 10(-7). The quinone methide derivative of p-cresol (PCQM) was prepared by Ag(1)O oxidation. Reaction of calf thymus DNA with PCQM produced four adducts 1: (18.5%), 2: (36.4%), 3: (29.0%) and 5: (16.0%) with a relative adduct level 1.6 x 10(-7). Rechromatography analyses indicates that DNA adducts 1-3 formed in HL-60 cells treated with p-cresol and after myeloperoxidase activation of p-cresol were similar to those formed by reaction of DNA with PCQM. This observation suggests that p-cresol is activated to a quinone methide intermediate in each of these activation systems. Taken together, these results suggest PCQM is the reactive intermediate leading to the formation of DNA adducts in HL-60 cells treated with p- cresol. Furthermore, the DNA adducts formed by PCQM may provide a biomarker to assess occupational exposure to toluene. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.