Vol. 11, No 1, 2004 pp. 1 - 4
UC 616.61(497)+616-006
ARISTOLOCHIC ACID- AND OCHRATOXIN A-DNA
ADDUCTS:
POSSIBLE MARKERS OF BALKAN ENDEMIC NEPHROPATHY
AND ASSOCIATED UROTHELIAL TUMORS?
Jean-Pierre Cosyns
Université Catholique de Louvain, Cliniques Universitaires St-Luc,
Department of Pathology, Brussels, Belgium
E-mail: cosyns@anps.ucl.ac.be
Summary. The etiology of Balkan endemic nephropathy (BN) is still
debated. The similar prevalence of the disease in immigrants and natives
in endemic areas points to environmental etiological factors. Viral agents,
selenium deficiency, cadmium, lead and long-term exposure to polycyclic
aromatic hydrocarbons and amines have received little support. By contrast,
BN is amazingly reminiscent of the findings characterizing aristolochic
acid (AA) and ochratoxin A (OTA) chronic intoxications. Both drugs have
nephrotoxic and carcinogenic activities providing a possible pathophysiological
clue for the develoment of the renal fibrosis and the urothelial malignancies
characterizing BN. Preliminary studies indicate that both toxic substances
may be food contaminants in endemic areas. Actual exposure of inhabitants
has recently been supported by the identification of AA- and OTA-related
DNA adducts in their renal tissue . Identification of these specific DNA
adducts in a large number of patients with BN and in control subjects remains
to be assessed. Molecular hallmarks like an A ? T transversion mutation
in the human p53 tumor suppressor gene characterizing AA-induced malignancy
may become additional disease markers which are presently missing in BN.
Key words: Balkan nephropathy, aristolochic acid, ochratoxin
A, interstitial nephritis, urothelial cancer
ARISTOLOHIČNA KISELINA I OHRATOKSIN A
DNK ADUKTI:
MOGUĆI MARKERI ENDEMSKE NEFROPATIJE I TUMORA
UROTELIJUMA
Kratak sadržaj: Etiologija endemske nefropatije (EN) još uvek nije
poznata. Slična prevalencija bolesti kod imigranata i starosedelaca endemskih
naselja upućuje na etiološku ulogu faktora sredine. Smatra se da virusi,
deficit selena, kadmijum, olovo i dugotrajno izlaganje policikličnim aromatičnim
ugljovodnicima i aminima nema etiološki značaj. Nasuprot tome, pažnju zaslužuje
hronična intoksikacija aristolohičnom kiselinom (AA) i ohratoksinom
A (OTA). Oba ova agensa imaju nefrotoksično i kancerogeno dejstvo sa patofiziološkom
osnovom za razvoj fibroze bubrega i karcinoma urotelijuma koji karakterišu
EN. Prethodna ispitivanja ukazuju da ove toksične supstance mogu biti prisutne
u hrani iz endemskih područja. Izloženost stanovništva bila je skoro potvrđena
prisustvom AA i OTA DNK-adukta u bubrežnom tkivu. Ostaje da se na velikom
broju obolelih ispita ovaj nalaz. Ključni molekulski nalaz A-T transverzione
mutacije humanog p53 tumorskog supresornog gena, koji karakteriše AA-izazvane
malignitete, može da bude dodatni marker bolesti, kakav danas ne postoji
u EN.
Ključne reči: Endemska nefropatija, aristolohična kiselina,
ohratoksin A, intersticijski nefritis, karcinom urotelijuma
