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Detection of DNA Adducts Formed by Aristolochic Acid in Renal Tissue from Patients with Chinese Herbs Nephropathy

Division of Molecular Toxicology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany [H. H. S., C. A. B., M. W.], and Departments of Pathology [J. P. C.] and Renal Diseases (C. v. Y. d. S.), University of Louvain Medical School, Cliniques Universitaires St-Luc, 10 Avenue Hippocrate, 1200 Bruxelles, Belgium

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 5.3/10⁷ 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.

¹ To whom requests for reprints should be addressed, at Division of Molecular Toxicology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Received 2/28/96. Accepted 3/25/96.

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