Naslov
P53 mutations as fingerprints for aristolochic acid - an environmental carcinogen in endemic (Balkan) nephropathy

Autori
Slade, Neda ; Brdar, Branko ; Zorić, Arijana ; Tomić, Karla ; Jakovina, Tratinčica ; Medverec, Zvonimir ; Dittrich, Damir ; Nikolić, Jovan ; Moriya, Masaaki ; Wu, Lin ; Grollman, Arthur P. ; Jelaković, Bojan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Recent advances in Balkan endemic nephropathy research / - : Interacademy Council of South Eastern Europe in collaboration with Serbian Academy of Sciences and Arts, 2009, 15-15

Skup
Recent advances in Balkan endemic nephropathy research

Mjesto i datum
Beograd, Srbija, 17.04.2009. - 18.04.2009

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Environmental carcinogen; Aristolochic acid; p53 mutations; DNA adducts; Endemic nephropathy; Aristolochic acid nephropathy

Sažetak
The activation of protooncogenes and inactivation of tumor suppressor genes are considered to be the main molecular events in the multistep process of carcinogenesis. Mutations of the TP53 tumor suppressor gene have been found in nearly all tumor types and are estimated to contribute to more than 50% of all cancers. Most mutations lead to the synthesis of highly stable, inactive proteins that accumulate in the nucleus of cancer cells. Alterations of codons 175, 248, 273 and 282 correspond to 19 % of all mutations and are considered general hot spot mutations. Dietary exposure to aristolochic acid (AA), an established nephrotoxin and human carcinogen found in all Aristolochia species was shown to be the causative agent of aristolochic acid nephropathy (previously called Chinese herbs nephropathy). This syndrome is characterized by proximal tubular damage, renal interstitial fibrosis, slow progression to the end stage renal disease and a high prevalence of upper urinary tract urothelial carcinoma (otherwise a highly unusual location). AA preferentially binds to purines in DNA and is associated with a high frequency of A → T transversions in the p53 gene. Rats treated with AA develop A:T → T:A mutations in codon 61 of c-H-ras gene. The pathological and clinical features of endemic (Balkan) nephropathy closely resemble those associated with aristolochic acid nephropathy except for the slower progression to end stage renal disease and longer cumulative period before the appearance of urothelial cancer. Recently, we reported the presence of AA-DNA adducts in renal cortex and A → T p53 mutations in tumor tissue of patients from Croatia and Bosnia with endemic nephropathy. These data support the hypothesis that dietary exposure to AA is a major risk factor for endemic (Balkan) nephropathy.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Javno zdravstvo i zdravstvena zaštita

POVEZANOST RADA