New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in human nephropathy and urinary tract tumor.
To find out whether ochratoxin A (OTA), citrinin (CIT), aristolochic acids (AA) are etiologic agents of Balkan endemic nephropathy (BEN) or Chinese herbal nephrotoxicity, and associated urinary tract tumor (UTT), we have compared (i) in human kidney cell culture, the DNA adduct formation and persistence of OTA/CIT and AA adducts (ii) analyzed DNA adduct in several tumors from human kidney suspected to be exposed to either OTA and CIT, or AAs (iii) analyzed OTA, CIT, and AA in food. In kidney cell cultures, formation of specific OTA-DNA adduct and AA-DNA adduct were detected in the same range (around 10 adducts/10(9) nucleotides) and were time- and dose-dependent. After 2 days all disappeared. DNA adduct related to OTA and CIT are found in human kidney tissues from Balkans, France, and Belgium whereas no DNA adducts related to AA could be found in any tumors of BEN patients from Croatia, Bulgaria, or Serbia. No DNA adduct was found in kidney biopsy or necropsy of the French women suspected to be exposed to AA. OTA and CIT are more frequently found in rural area. AA was never detected. All these plead for implication of mycotoxins, especially OTA, in BEN and UTT.
Pfohl-Leszkowicz
Annie
A
Laboratoire Génie chimique, UMR CNRS/INPT/UPS 5503, INP/ENSA Toulouse, Auzeville-Tolosane, France. leszkowicz@ensat.fr
Tozlovanu
Mariana
M
Manderville
Richard
R
Peraica
Maja
M
Castegnaro
Marcel
M
Stefanovic
Vladislav
V
D000368:Aged; D000369:Aged, 80 and over; D019440:Anti-Obesity Agents / Q000032:analysis; D034341:Aristolochic Acids / Q000032:analysis / Q000633:toxicity* / Q000652:urine; D001449:Balkan Nephropathy / Q000139:chemically induced*; D001530:Belgium; D002031:Bulgaria; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002953:Citrinin / Q000032:analysis / Q000633:toxicity / Q000652:urine; D017523:Croatia; D018736:DNA Adducts / Q000032:analysis / Q000378:metabolism; D005260:Female; D005504:Food Analysis; D005602:France; D006801:Humans; D007668:Kidney / Q000737:chemistry; D007680:Kidney Neoplasms / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009183:Mycotoxins / Q000032:analysis / Q000633:toxicity*; D009793:Ochratoxins / Q000032:analysis / Q000633:toxicity / Q000652:urine; D014571:Urologic Neoplasms / Q000139:chemically induced* / Q000737:chemistry; D015022:Yugoslavia
D019440:Anti-Obesity Agents; D034341:Aristolochic Acids; D018736:DNA Adducts; D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A; D002953:Citrinin; C000228:aristolochic acid I