Yun Byeong Hwa, Guo Jingshu, Turesky Robert J
Masonic Cancer Center and Department of Medicinal Chemistry, University of Minnesota, 2231 6th St. SE, Minneapolis, MN 55455, USA.
Toxics. 2018 Jun 1;6(2):30. doi: 10.3390/toxics6020030.
The measurement of DNA adducts provides important information about human exposure to genotoxic chemicals and can be employed to elucidate mechanisms of DNA damage and repair. DNA adducts can serve as biomarkers for interspecies comparisons of the biologically effective dose of procarcinogens and permit extrapolation of genotoxicity data from animal studies for human risk assessment. One major challenge in DNA adduct biomarker research is the paucity of fresh frozen biopsy samples available for study. However, archived formalin-fixed paraffin-embedded (FFPE) tissues with clinical diagnosis of disease are often available. We have established robust methods to recover DNA free of crosslinks from FFPE tissues under mild conditions which permit quantitative measurements of DNA adducts by liquid chromatography-mass spectrometry. The technology is versatile and can be employed to screen for DNA adducts formed with a wide range of environmental and dietary carcinogens, some of which were retrieved from section-cuts of FFPE blocks stored at ambient temperature for up to nine years. The ability to retrospectively analyze FFPE tissues for DNA adducts for which there is clinical diagnosis of disease opens a previously untapped source of biospecimens for molecular epidemiology studies that seek to assess the causal role of environmental chemicals in cancer etiology.
DNA加合物的测量为了解人类接触遗传毒性化学物质提供了重要信息，可用于阐明DNA损伤和修复机制。DNA加合物可作为生物标志物，用于种间比较前致癌物的生物有效剂量，并允许从动物研究中推断遗传毒性数据以进行人类风险评估。DNA加合物生物标志物研究的一个主要挑战是可用于研究的新鲜冷冻活检样本匮乏。然而，具有疾病临床诊断的存档福尔马林固定石蜡包埋（FFPE）组织通常是可获得的。我们已经建立了可靠的方法，在温和条件下从FFPE组织中回收无交联的DNA，这使得通过液相色谱-质谱法对DNA加合物进行定量测量成为可能。该技术用途广泛，可用于筛查由多种环境和饮食致癌物形成的DNA加合物，其中一些是从在室温下保存长达九年的FFPE块切片中提取的。对有疾病临床诊断的FFPE组织进行DNA加合物回顾性分析的能力，为分子流行病学研究开辟了一个以前未开发的生物样本来源，这些研究旨在评估环境化学物质在癌症病因中的因果作用。
