Chem Res Toxicol. 2019 Mar 18;32(3):397-399. doi: 10.1021/acs.chemrestox.8b00359. Epub 2019 Jan 8.
Chronic exposure to aristolochic acids (AAs) from Aristolochia plants is one of the major causes of nephropathy and cancer of the kidney and forestomach. However, the organotropic activities of AAs remain poorly understood. In this study, using LC-MS/MS coupled with a stable isotope-dilution method, we rigorously quantitated for the first time the organ-specific dosage- and time-dependent formation of DNA-AA adducts in the tumor target and nontarget organs of AA-I-treated rats. The results support the proposal that the DNA adduct level is a major contributor to the observed organotropic activities of AAs.
长期接触马兜铃酸(AAs)是导致肾病和肾及胃肿瘤的主要原因之一。然而,AA 的器官靶向活性仍知之甚少。在这项研究中,我们首次使用 LC-MS/MS 结合稳定同位素稀释法,严格定量了 AA-I 处理大鼠肿瘤靶器官和非靶器官中 DNA-AA 加合物的剂量和时间依赖性形成。结果支持了 DNA 加合物水平是 AA 观察到的器官靶向活性的主要贡献者的观点。