Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects
Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects
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DOI：
10.1164/ajrccm.163.6.2006056
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发表时间：
2001-05-01
影响因子：
24.7
通讯作者：
Mutti, A
中科院分区：
文献类型：
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作者：
Bergamaschi, E;De Palma, G;Mutti, A
在24名健康非吸烟者中研究了NAD（P）H：醌氧化还原酶（NQO 1）和谷胱甘肽-S-转移酶mu-1（GSTM 1）的遗传多态性在O-3诱导的急性效应反应中的作用。在骑行之前和之后，每个受试者进行肺量测定测试，并提供血液样本用于测量克拉拉细胞蛋白CC 16。NQO 1和GSTM 71多态性的特点是聚合酶链反应为基础的方法。外周血白细胞DNA中也检测到8-羟基-2 '-脱氧鸟苷（8-OHdG）加合物。在O-3 > 80 ppb下的骑行导致肺功能测试的显著降低和血清CC 16水平的增加，分别与呼吸功能的轻度损害和肺上皮通透性的增加一致。而NQO 1 wt和GSTM 1 null受试者在急性O-3暴露后表现出功能变化和血清CC 16升高，其他单倍型的人血清CC 16升高，但肺功能测试没有变化。偏相关分析显示，NQO 1 wt和GSTM 1 null个体的功能减退和血清CC 16水平升高与O3水平密切相关，而其他单倍型个体的相关性不明显。O-3和氢醌之间的反应速率增加与该“敏感”组中O-3暴露后8-OHdG的较大增加一致。
The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase mu -1 (GSTM1) in the responsiveness to O-3-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O-3 varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM71 polymorphisms were characterized by polymerase chain reaction-based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O-3 > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O-3 exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O-3 levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O-3 and hydroquinones would be consistent with the greater increase in 8-OHdG after O-3 exposure in this "susceptible" group.