Schmeiser H H, Bieler C A, Wiessler M, van Ypersele de Strihou C, Cosyns J P
Division of Molecular Toxicology, German Cancer Research Center, Heidelberg, Germany.
Cancer Res. 1996 May 1;56(9):2025-8.
A unique type of rapidly progressive renal fibrosis, designated Chinese herbs nephropathy (CHN), has been described in young Belgian women who had followed a slimming regimen including recently introduced Chinese herbs (Stephania tetrandra and Magnolia officinalis). Aristolochic acid (AA), a known nephrotoxin and carcinogen, was suspected as its causal factor. To substantiate this hypothesis, renal tissue from five patients with CHN and six patients with other renal diseases was analyzed for the presence of AA-derived DNA adducts, a described biomarker of AA exposure associated with its carcinogenic and mutagenic activity. Using the 32P-postlabeling method, a major distinct DNA adduct spot was found in all five cases of CHN and identified by cochromatographic analyses with authentic markers as the deoxyadenosine adduct of AA-I [7-(deoxyadenosin-N6-yl)-aristolactam I], the major component of the plant extract AA. This DNA adduct was absent in the six control cases. The 7-(deoxyadenosin-N6-yl)-aristolactam I adduct levels in CHN ranged from 0.7 to 5.3/10(7) nucleotides. Our data demonstrate that AA is implicated in CHN. They suggest a mechanism for the urothelial atypia and cancers observed in this disease and raise the possibility that a DNA mutation is responsible for the kidney-destructive fibrotic process.
一种独特的快速进展性肾纤维化，被称为中草药肾病（CHN），已在年轻的比利时女性中被描述，她们遵循了包括最近引入的中草药（防己和厚朴）的减肥方案。马兜铃酸（AA），一种已知的肾毒素和致癌物，被怀疑是其致病因素。为了证实这一假设，对5例CHN患者和6例其他肾脏疾病患者的肾组织进行了分析，以检测AA衍生的DNA加合物的存在，这是一种与AA的致癌和诱变活性相关的已描述的AA暴露生物标志物。使用32P后标记法，在所有5例CHN病例中均发现了一个主要的独特DNA加合物斑点，并通过与真实标记物的共色谱分析鉴定为AA-I [7-（脱氧腺苷-N6-基）-马兜铃内酰胺I]的脱氧腺苷加合物，这是植物提取物AA的主要成分。在6例对照病例中未发现这种DNA加合物。CHN中7-（脱氧腺苷-N6-基）-马兜铃内酰胺I加合物水平在0.7至5.3/10（7）个核苷酸之间。我们的数据表明AA与CHN有关。它们提示了在这种疾病中观察到的尿路上皮异型增生和癌症的一种机制，并增加了DNA突变是导致肾脏破坏性纤维化过程的原因的可能性。
