DETECTION OF DNA-ADDUCTS FORMED BY ARISTOLOCHIC ACID IN RENAL TISSUE FROM PATIENTS WITH CHINESE HERBS NEPHROPATHY

A unique type of rapidly progressive renal fibrosis, designated Chines e herbs nephropathy (CHN), has been described in young Belgian women w ho had followed a slimming regimen including recently introduced Chine se herbs (Stephania tetrandra and Magnolia officinalis). Aristolochic acid (AA), a known nephrotoxin and carcinogen, was suspected as its ca usal factor, To substantiate this hypothesis, renal tissue from five p atients with CHN and six patients with other renal diseases was analyz ed for the presence of AA-derived DNA adducts, a described biomarker o f AA exposure associated with its carcinogenic and mutagenic activity, Using the P-32-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-N-6-yl)-aristolactam I], the major component of the plant extract AA, This DNA adduct was absent in the six control cases, The 7-(deoxyadenosin-N-6-yl) -aristolactam I adduct levels in CHN ran ged 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 proce ss.