Department of Preventive Medicine and Community Health, 700 Harborside Drive, University of Texas Medical Branch, Galveston, TX 77555-1110, USA.
Int J Hyg Environ Health. 2010 Jan;213(1):32-9. doi: 10.1016/j.ijheh.2009.09.002. Epub 2009 Oct 8.
A variety of biomarkers have been used to monitor exposed populations to determine potential health hazards from their exposure to environmental toxic agents. However, the majority of these biomarkers have been focused onto the identification of biological damage from the exposure. Therefore, there is a need to develop functional biomarkers that can identify exposure-induced functional deficiencies. More importantly, these deficiencies should be positioned along pathways that are responsible for the development of specific diseases. One of such pathways belongs to the extensive and complex DNA-repair machinery. The machinery thus becomes a large target for damage from environmental toxic agents. The hypothesis is that damage to any component of a repair pathway will interfere with the pathway-specific repair activities. Therefore, when cells from exposed populations are challenged with a DNA-damaging agent in vitro, the in vivo exposure-induced repair deficiency will be dramatically amplified and the deficiency will be detectable in a challenge assay as increased chromosome aberrations, micronuclei or un-repaired DNA strand breaks. The challenge assay has been used in different laboratories to show that a variety of exposed populations (with exposure to air pollutants, arsenic, benzene, butadiene, cigarette smoke, incense smoke, lead, mercury, pesticides, uranium or xylene but not to low concentrations of air pollutants or butadiene) expressed abnormal challenge response. The predicted health consequences of some of these studies have also been validated. Therefore, the challenge assay is a useful functional biomarker for population studies. Details of the challenge assay and its application will be presented in this review.
已经有多种生物标志物被用于监测暴露人群，以确定他们接触环境有毒物质可能带来的健康危害。然而，这些生物标志物大多集中在识别暴露带来的生物损伤上。因此，有必要开发能够识别暴露引起的功能缺陷的功能性生物标志物。更重要的是，这些缺陷应该定位在负责特定疾病发展的途径上。其中一条途径属于广泛而复杂的 DNA 修复机制。因此，该机制成为环境有毒物质损伤的一个大目标。假设任何修复途径的组件受损都会干扰途径特异性的修复活动。因此，当暴露人群的细胞在体外受到 DNA 损伤剂的挑战时，体内暴露引起的修复缺陷将被显著放大，并且在挑战试验中可以检测到增加的染色体畸变、微核或未修复的 DNA 链断裂。该挑战试验已在不同实验室中使用，以表明各种暴露人群（接触空气污染物、砷、苯、丁二烯、香烟烟雾、熏香烟雾、铅、汞、农药、铀或二甲苯，但不接触低浓度空气污染物或丁二烯）表现出异常的挑战反应。其中一些研究的预测健康后果也已得到验证。因此，挑战试验是人群研究的一种有用的功能性生物标志物。本综述将介绍挑战试验及其应用的详细信息。
