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Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract Tumours

Annie Pfohl-Leszkowicz1

Lab Chemical Engineering, Department Bioprocess & Microbial System, University of Toulouse, Auzeville-Tolosane, France1

This content is open access.

Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 60, Issue 4, Pages 465–483, ISSN (Print) 0004-1254, DOI: 10.2478/10004-1254-60-2009-2000, January 2010

Publication History

Published Online:
2010-01-07

Ochratoxin A and Aristolochic Acid Involvement in Nephropathies and Associated Urothelial Tract Tumours

This review addresses the unresolved aetiology of several nephropathies and associated upper tract tumours diagnosed all over the world, but especially in the Balkan regions. Studies conducted over the last 35 years point to mycotoxins, mainly ochratoxin A (OTA) as the main culprit. Recent theories however have implicated aristolochic acids (AA). The aim of this review is to put forward arguments in favour of the mycotoxin theory and to show the incoherence of the AA theory. It discusses the differences between the epidemiology of Balkan endemic nephropathy (BEN) and aristolochic acid nephropathy (AAN); OTA and AA carcinogenicity; clinical and pathological effects induced by OTA and AA; sources of OTA contamination (food, air, drinking water); OTA- and AA-DNA adduct formation; the role of genetic polymorphisms; and the risk for young children.

Saznanja o ulozi mikotoksina i aristolohične kiseline u nefropatijama i pridruženim tumorima mokraćnog sustava

Etiologija dijela nefropatija i srodnih im tumora gornjeg dijela mokraćnog sustava koji se dijagnosticiraju diljem svijeta, a posebice na prostoru Balkana, još nije razjašnjena. Rezultati istraživanja provedenih zadnjih 35 godina upućuju na mikotoksine, a posebice okratoksin A (OTA), kao glavne uzročnike. U posljednje vrijeme raspravlja se i o mogućoj ulozi aristolohičnih kiselina (AA). Svrha ovoga preglednog rada jest obrazložiti argumente koji govore u prilog uključenosti mikotoksina kao čimbenika odgovornih za nastanak navedenih bolesti te rasvijetliti zablude oko teze koja govori u prilog uključenosti AA kao mogućeg uzročnika. U članku se raspravlja o razlici između (i) epidemiologije endemske (balkanske) nefropatije (BEN) i nefropatije uzrokovane pod utjecajem aristolohične kiseline (AAN), (ii) karcinogenosti OTA i AA, (iii) kliničkim i patološkim učincima izazvanim pod utjecajem OTA i AA, (iv) izvorima kontaminacije s OTA (hrana, zrak, pitka voda), (v) nastanku DNA-adukata pod utjecajem OTA ili AA, (vi) ulozi genskog polimorfizma i (vii) riziku za malu djecu.

Keywords: aetiology; contamination; DNA adduct; genetic polymorphism; pathological effects; urothelial cancer

Keywords: bubreg; DNA-adukt; etiologija; genski polimorfizam; karcinom mokraćnog sustava; kontaminacija; patološki učinci

  • Stefanović V. Diagnostic criteria for endemic (Balkan) nephropathy. In: Strahinjić S, Stefanović V, edtors. Current research in endemic (Balkan) nephropathy. Niš: University Press; 1983. p. 351-63.

  • Tanchev Y, Evstatiev ZV, Dorosiev G, Pencheva ZH, Zvetkov G. Prouchavaniia na nefrititev v vrachanska okolia. [Study on nephritis in the region of Vratza, in Bulgarian]. Savr Med 1956;7:14-29.

  • Danilovic V, Djurisic M, Mokranjac M, Stojimirovic B, Zivojinovic J, Stojakovic P. Chronic nephritis due to lead poisoning by digestive route (flour) [Néphrites chroniques provoquées par l'intoxication au plomb par voie digestive (farine), in French]. Presse Méd 1957;65:2039-40.

  • Polenaković M, Stefanović V. Balkan nephropathy. In: Cameron JS, Davison AM, Grunfeld JP, Kerr D, Ritz E, editors. Oxford textbook of clinical nephrology. 1st ed. Oxford: Oxford University Press; 1992. p. 857-66.

  • Chernozemsky IN, Stoyanov IS, Petkova-Bocharova TK, Nicolov IG, Draganov IV, Stoichev II, Tanchev Y, Naidenov D, Kalcheva ND. Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in Vratza district, Bulgaria. Int J Cancer 1977;19:1-11. [PubMed] [CrossRef]

  • Cukuranović R, Ignjatović M, Stefanović V. Urinary tract tumors and Balkan nephropathy in the South Morava River basin. Kidney Int 1991;40(Suppl 34):S80-4.

  • Miletić-Medved M, Domijan AM, Peraica M. Recent data on endemic nephropathy and related urothelial tumors in Croatia. Wien Klin Wochensch 2005;117:604-9. [CrossRef]

  • Ceović S, Hrabar A, Radonić M. An etiological approach to Balkan endemic nephropathy based on the investigation of two genetically different populations. Nephron 1985;40:175-9. [PubMed]

  • Janković S, Marinković J, Radovanović Z. Survival of the upper-urothelial-cancer patients from the Balkan nephropathy endemic and nonendemic areas. Eur Urol 1988;15:59-61. [PubMed]

  • Nikolić J, Djokić M, Crnomarković D, Marinković J. Upper urothelial tumors and Balkan endemic nephropathy-dose responsible diseases. Facta Univ Ser Med Biol 2002;9:114-8.

  • Akhmeteli MA. Epidemiology of endemic nephropathy. In: Proceedings of the Second International Symposium on Endemic Nephropathy; 9-12 Nov 1972; Sofia, Bulgaria. Sofia: Bulgarian Academy of Sciences; p. 19-23.

  • Krogh P. Mycotoxic porcine nephropathy - a possible model for Balkan (endemic) nephropathy. In: Proceedings of the Second International Symposium on Endemic Nephropathy; 9-12 Nov 1972; Sofia, Bulgaria. Sofia: Bulgarian Academy of Sciences; p. 266-77.

  • Hranjec T, Kovac A, Kos J, Mao W, Chen JJ, Grollman AP, Jelakovic B. Endemic nephropathy: the case for chronic poisoning by Aristolochia. Croat Med J 2005;46:116-25. [PubMed]

  • Batuman V. Fifty years of Balkan endemic nephropathy: daunting questions, elusive answers. Kidney Int 2006;69:644-6. [PubMed] [CrossRef]

  • Cosyns JP, Goebbels RM, Liberton V, Schmeiser HH, Bieler CA, Bernard AM. Chinese herbs nephropathy associated slimming regimen induces tumours in the forestomach but no interstitial nephropathy in rats. Arch Toxicol 1998;72:738-43. [CrossRef] [PubMed]

  • Long DT, Voice TC. Role of exposure analysis in solving the mystery of Balkan endemic nephropathy. Croat Med J 2007;48:300-11. [PubMed]

  • Peraica M, Domijan A-M, Saric M. Mycotoxic and aristolochic acid theories of the development of endemic nephropathy. Arh Hig Rada Toksikol 2008;59:59-65.

  • Austwick PK. Balkan nephropathy. Practitioner 1981;225:1031-8. [PubMed]

  • Cui M, Liu ZH, Qiu Q, Li H, Li LS. Tumour induction in rats following exposure to short-term high dose aristolochic acid I. Mutagenesis 2005;20:45-9. [PubMed] [CrossRef]

  • Krasteva ME, Georgieva EI. Germline p53 single-base changes associated with Balkan endemic nephropathy. Biochem Biophys Res Commun 2006;342:562-7.

  • De Broe ME. On a nephrotoxic and carcinogenic slimming regimen. Am J Kidney Dis 1999;33:1171-3. [PubMed]

  • Xue X, Xiao Y, Gong L, Guan S, Liu Y, Lu H, Qi X, ZhangY, Li Y, Wu X, Ren J. Comparative 28-day repeated oral toxicity of Longdan Xieganwan, Akebia trifoliate (Thunb.) Koidz, Akebia quinata (Thunb.) Decne and Caulis aristolochiae manshuriensis in mice. J Ethonopharmacol 2008;119:87-93. [CrossRef]

  • Qiu Q, Liu ZH, Chen HP, Yin HL, Li LS. Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats. Acta Pharmacol Sin 2000;21:1129-35. [PubMed]

  • Liu MC, Maruyama S, Mizuno M, Morita Y, Hanaki S, Yuzawa Y, Matsuo S. The nephrotoxicity of Aristolochia manshuriensis in rats is attributable to its aristolochic acids. Clin Exp Nephrol 2003;7:186-94. [CrossRef]

  • Vanherweghem LJ. Missue of herbal remedies: the case of an outbreak of terminal renal failure in Belgium (Chinese herbs nephropathy). J Altern Complement Med 1998;4:9-13. [CrossRef] [PubMed]

  • Meyer MM, Chen TP, Bennett WM. Chinese herb nephropathy. BUMC Proc 2000;13:334-7.

  • Boorman GA. Toxicology and carcinogenesis studies of ochratoxin A (CAS No 303-47-9) in F344/N rats (gavage studies). National Toxicology Programme, Technical Report Series 358, 1989 [displayed 12 November 2009]. Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr358.pdf

  • Lock EA, Hard GC. Chemically induced renal tubule tumours in the laboratory rat and mouse: review of the NCI/NTP data base and categorization of renal carcinogens based on mechanistic information. Crit Rev Toxicol 2004;34:211-99. [CrossRef]

  • Son WC, Kamino K, Lee YS, Kang KS. Strain-specific mammary proliferative lesion development following lifetime oral administration of ochratoxin A in DA and Lewis rats, Int. J Cancer 2003;105:305-11.

  • Castegnaro M, Mohr U, Pfohl-Leszkowicz A, Esteve J, Steinmann J, Tillmann T, Michelon J, Bartsch H. Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction. Int J Cancer 1998;77:70-5. [CrossRef] [PubMed]

  • Pfohl-Leszkowicz A, Pinelli E, Bartsch H, Mohr U, Castegnaro M. Sex- and strain-specific expression of cytochrome P450s in ochratoxin A-induced genotoxicity and carcinogenicity in rats. Mol Carcinogen 1998;23:76-85.

  • Mantle P, Kulinskaya E, Nestler S. Renal tumourigenesis in male rats in response to chronic dietary ochratoxin A. Food Addit Contam 2005;22(Suppl 1):58-64. [PubMed] [CrossRef]

  • Mantle PG. Minimum tolerable exposure period and maximum threshold dietary intake of ochratoxin A for causing renal cancer in Dark Agouti rats. Food Chem Toxicol 2009;47:2419-24. [PubMed] [CrossRef]

  • Pfohl-Leszkowicz A, Castegnaro M. Further arguments in favour of direct covalent binding of Ochratoxin A (OTA) after metabolic biotransformation. Food Addit Contam 2005;22(Suppl 1):75-87. [CrossRef]

  • Mengs U. Tumour induction in mice following exposure to aristolochic acid. Arch Toxicol 1988;61:504-5. [CrossRef] [PubMed]

  • EMEA, European Medicines Agency, Evaluation of Medicines for Human Use. Public Statement on the risks associated with the use of herbal products containing Aristolochia species. [displayed 12 November 2009]. Available at http://www.emea.europa.eu/pdfs/human/hmpc/13838105en.pdf

  • Debelle FD, Nortier JL, De Prez EG, Garbar CH, Vienne AR, Salmon IJ, Deschodt-Lanckman MM, Vanherweghem JL. Aristolochic acids induce chronic renal failure with interstitial fibrosis in salt depleted rats. J Am Soc Nephrol 2002;13:431-6. [PubMed]

  • Mengs U, Lang W, Poch JA. The carcinogenic action of aristolochic acid in rats. Arch Toxicol 1982;51:107-19. [CrossRef]

  • Mengs U. On the histopatogenesis of rat forestomach carcinoma caused by aristolochic acid. Arch Toxicol 1983;52:209-20. [PubMed] [CrossRef]

  • Cosyns JP, Dehoux JP, Guiot Y, Goebbels RM, Robert A, Bernard AM, van Ypersele de Strihou C. Chronic aristolochic acid toxicity in rabbits: a model of Chinese herbs nephropathy? Kidney Int 2001;59:2164-73.

  • Chang HR, Lian JD, Lo CW, Chang YC, Yang MY, Wang CJ. Induction of urothelial proliferation in rats by aristolochic acid through cell cycle progression via activation of cyclin D1/cdk4 and cyclin E/cdk2. Food Chem Toxicol 2006;44:28-35.

  • International Agency for Research on Cancer (IARC). Ochratoxin A. In: IARC Monographs on the evaluation of carcinogenic risks to humans. Vol 56. Geneva: IARC; 1993. p. 489-521.

  • Pfohl-Leszkowicz A, Manderville R. Ochratoxin A: an overview on toxicity and carcinogenicity in animals and humans. Mol Nutr Food Res 2007;51:61-99. [CrossRef]

  • Radavanović Z, Janković S, Jevremović I. Incidence of tumours of urinary organs in a focus of Balkan endemic nephropathy. Kidney Int 1991;40(Suppl 34):75-7.

  • Stoev S, Hald B, Mantle PG. Porcine nephropathy in Bulgaria: a progressive syndrome of complex or uncertain (mycotoxin) aetiology. Vet Rec 1998;142:190-4. [CrossRef] [PubMed]

  • Stoev S, Grozeva N, Hald B. Ultrastructural and toxicological investigations in spontaneous cases of poricine nephropathy in Bulgaria. Vet Arhiv 1998;68:39-49.

  • Stoev S, Paskalev M, MacDonald S, Mantle PG. Experimental one year ochratoxin A toxicosis in pigs. Exp Toxicol Pathol 2002;53:481-7. [PubMed] [CrossRef]

  • Stoev SD. Complex etiology, prophylaxis and hygiene control in mycotoxic nephropathies in farm animals and humans. Int J Mol Sci 2008;9:578-605. [CrossRef] [PubMed]

  • Ceci E, Bozzo G, Bonerba E, Di Pinto A, Tantillo MG. Ochratoxin A detection by HPLC in target tissues of swine and cytological and histological analysis. Food Chem 2007;105:364-8. [CrossRef]

  • Milićević D, Jurić V, Stefanović S, Jovanović M, Janković S. Survey of slaughtered pigs for occurrence of ochratoxin A and porcine nephropathy in Serbia. Int J Mol Sci 2008;9:2169-83. [PubMed] [CrossRef]

  • Stoev SD, Vitanov S, Naguelov G, Petkova-Bocharova T, Creppy EE. Experimental mycotoxic nephropathy in pigs provoked by a mouldy diet containing ochratoxin A and penicillic acid. Vet Res Commun 2001;25:205-33. [PubMed] [CrossRef]

  • Stoev SD, Stefanov S, Denev S, Radić B, Domijan A-M, Peraica M. Experimental mycotoxicosis in chickens induced by ochratoxin A and penicillic acid and intervention by natural plant extracts. Vet Res Commun 2004;28:727-46. [CrossRef] [PubMed]

  • Diaz CT, Sogbe E, Ascanio E, Hernandez M. Ochratoxin A and fumonisin B1 natural interaction in pigs. Clinical and pathological studies. Rev Cient Fac Cien V 2001;11:314-21.

  • Domijan A-M, Želježić D, Kopjar N, Peraica M. Standard and Fpg-modifed comet assay in kidney cells of ochratoxin A- and fumonisin B1-treated rats. Toxicology 2006;222:53-9. [CrossRef]

  • Kubena LF, Edrington TS, Harvey RB, Phillips TD, Sarr AB, Rottinghaus GE. Individual and combined effects o fumonisin B1 present in Fusarium moniliforme culture material and diacetoxuscirpenol or ochratoxin A in turkey poults. Poultry Sci 1997;76:256-64.

  • Bernhoft A, Keblys M, Morrison E, Larsen HJS, Flaoyen A. Combined effects of selected Penicillium mycotoxins on in vitro proliferation of porcine lymphocytes. Mycopathologia 2004;158:441-50. [CrossRef]

  • Koshinsky HA, Khachatourians GG. Other forms of mycotoxicoses: the effects of mycotoxin combinations. In: Hui YH, editor. Handbook of Foodborne Diseases. Vol. 2. New York (NY): Marcel Dekker Inc.; 1994. p. 463-520.

  • Pfohl-Leszkowicz A, Molinie A, Tozlovanu M, Manderville RA. Combined toxic effects of ochratoxin A and citrinin, in vitro and in vivo. In: Siantar DP, Trucksess MW, Scott PM, Herman EM, editors. Food contaminants; mycotoxins and food allergen. ACS Symposium Series. Vol. 1001. Washington (DC): American Chemical Society; 2008. p. 56-80.

  • Pfohl-Leszkowicz A, Tozlovanu M, Manderville R, Peraica M, Castegnaro M, Stefanovic V. New molecular and field evidences for the implication of mycotoxins but not aristolochic acid in Human Nephropathy and Urinary tract tumor. Mol Nutr Food Res 2007;51:1131-46. [CrossRef]

  • Pfohl-Leszkowicz A, Grosse Y, Castegnaro M, Petkova- Bocharova T, Nicolov IG, Chernozemsky IN, Bartsch H, Betbeder AM, Creppy EE, Dirheimer G. Ochratoxin A related DNA adducts in urinary tract tumours of Bulgarian subjects. In: Phillips D, Castegnaro M, Bartsch H, editors. Postlabelling methods for detection of DNA adducts. IARC Scientific Publication 124. Lyon: IARC; 1993. p. 141-8.

  • Wiessler M. DNA adducts of pyrrolizidine alkaloids, nitroimidazoles and aristolochic acid. In: Hemminki K, Dipple A, Shuker DBG, Kadulubar FF, editors. DNA adducts: identification and biological significance. IARC Scientific Publication 125. Lyon: IARC; 1995. p. 165-77.

  • Manderville R, Pfohl-Leszkowicz A. Bioactivation and DNA adduction as a rationale for ochratoxin A carcinogenesis. World Mycotoxin J 2008;1:357-67. [CrossRef]

  • Tozlovanu M, Faucet-Marquis V, Pfohl-Leszkowicz A, Manderville R A. Genotoxicity of the hydroquinone metabolite of ochratoxin A: Structure-activity relationships for covalent DNA adduction. Chem Res Toxicol 2006;19:1241-7. [CrossRef]

  • Faucet V, Pfohl-Leszkowicz A, Dai J, Castegnaro M, Manderville RA. Evidence for covalent DNA adduction by Ochratoxin A following chronic exposure to rat and subacute exposure to pig. Chem Res Toxicol 2004;17:1289-96. [PubMed] [CrossRef]

  • Faucet-Marquis V, Tozlovanu M, Richard A, Manderville RA, Mantlen P, Pfohl-Leszkowicz A. Evidence by LC ms/ms of the presence of 2'-deoxyguanosine-carbon 8-bound ochratoxin A in kidney DNA of rat fed OTA. In: EEMS 38th Annual Meeting, Environmental Mutagens and Health; 21-25 Sept 2008. Cavtat. Program and Abstracts p. 131.

  • Mantle P, Faucet-Marquis V, Manderville R, Squillaci B, Pfohl-Leszkowicz A. Structures of covalent adducts between DNA and ochratoxin A: a new factor in debate about genotoxicity and human risk assessment. Chem Res Toxicol 2010; (in press) (DOI 10.1021/tx900295a) [CrossRef]

  • Schmeiser HH, Biehler CA, Wiessler M, van Ypersele de Strihou C, Cosyns JP. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese Herbs nephropathy. Cancer Res 1996;56:2025-8. [PubMed]

  • Biehler CA, Stiborova M, Wiessler M, Cosyns JP, van Ypersele de Strihou C, Schmeiser HH. 32P-psot labeling analysis of DNA adducts formed by aristolochic acid in tissues from patients with Chinese herbs nephropathy. Carcinogenesis 1997;18:1063-7. [CrossRef]

  • Arlt VM, Pfohl-Leszkowicz A, Cosyns JP, Schmeiser HH. Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patient with Chinese herbs nephropathy. Mutat Res 2001;494:143-50. [PubMed] [CrossRef]

  • Arlt VM, Ferluga D, Stirborova M, Pfohl-Leszkowicz A, Vukelic M, Ceovic S, Schmeiser HH, Cosyns JP. Is aristolochic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer? Int J Cancer 2002;101:500-2. [CrossRef] [PubMed]

  • Grollman AP, Shibutani S, Moriya M, Miller F, Wu L, Moll U, Suzuki N, Fernandes A, Rosenquist T, Medverec Z, Jakovina K, Brdar B, Slade N, Turesky RJ, Goodenough AK, Rieger R, Vukelić M, Jelaković B. Acid aristolochic and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci USA 2007;104:12129-34. [CrossRef]

  • Arlt VM, Alunni-Perret V, Quatrehomme G, Ohayon P, Albano L, Gaid H, Michiels JF, Meyrier A, Cassuto E, Wiessler M, Schmeiser HH, Cosyns JP. Aristolochic acid (AA-)-DNA addcut as marker of AA exposure and risk factor for AA nephropathy-associated cancer. Int J Cancer 2004;111:977-80. [CrossRef]

  • Stengel B, Jones E. Insuffisance rénale terminale associée à la consommation d'herbes chinoises en France [End-stage renal failure associated with chinese herbs in France, in French]. Néphrologie 2004;19:15-20.

  • Pfohl-Leszkowicz A. Formation, persistence and significance of DNA adduct formation in relation to some pollutants from a board perspective. Adv Toxicol 2008;2:183-240. [CrossRef]

  • Malak J. Chinese herb nephropathy is not a (dex)fenfluramine nephropathy but a serotonin nephropathy. J Altern Complement Med 1998;4:131-5. [CrossRef] [PubMed]

  • Atanasova SY, von Ahsen N, Toncheva D, Dimitrov TG, Oellerich M, Armstrong VW. Genetic polymorphisms of cytochrome P450 among patients with Balkan endemic nephropathy (BEN). Clin Biochem 2005;38:223-8.

  • Givens R, Lin Y, Dowling A, Thummel KE, Lamba JK, Schuetz EG, Stewart PW, Watkins PB. CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. J Appl Physiol 2003;95:1297-1300.

  • Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002;54:1271-94.

  • Plant N. The human cytochrome P450 sub-family: Transcriptional regulation, inter-individual variation and interaction networks. Biochim Biophys Acta 2007;1770:478-88.

  • Nikolov IG, Chernozemsky IN, Idle JR. Genetic predisposition to Balkan endemic nephropathy: Ability to hydroxylate debrisoquine as a host risk factor. In: Bartsch H, Dirheimer G, Categnaro M, Pleština R, Chernozemsky IN, editors. Mycotoxins, endemic nephropathy and urinary tract tumours. IARC Scientific Publication 115. Lyon: IARC; 1991. p. 289-96.

  • Schaaf GJ, Nijmeijer SM, Maas RFM, Roestenberg P, de Groene EM, Fink-Gremmels J. The role of oxidative stress in the ochratoxin A mediated toxicity in proximal tubular cells. Biochim Biophys Acta 2002;1588:149-58.

  • El Adlouni C, Pinelli E, Azemar B, Zaoui D, Beaune P, Pfohl-Leszkowicz A. Role of CYP 2C and microsomal glutathione-S-transferase in modulating susceptibility to ochratoxin A genotoxicity. Environ Mol Mutagen 2000;35:123-31. [CrossRef]

  • Katoh T. Application of molecular biology to occupational health field-the frequency of gene polymorphism of cytochrome P450 1A1 and glutathione S-transferase M1 in patient with lung, oral and urothelial cancer. J UOEH 1995;17:271-8.

  • Aktas D, Ozen H, Atsu N, Tekin A, Sozen S, Tuncbilek E. Glutathione-S-transferase M1 gene polymorphism in bladder cancer patient. A marker for invasive bladder cancer? Cancer Genet Cytogenet 2001;125:1-4. [CrossRef]

  • Longuemaux S, Deloménie C, Gallou C, Méjean A, Vincent- Viry M, Bouvier R, Droz D, Krishnamoorthy R, Galteau MM, Junien C, Béroud C, Dupret JM. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Cancer Res 1999;59:2903-8. [PubMed]

  • Steinhoff C, Franke FH, Golka, K, Their R, Romer HC, Rotzel C, Ackerman R, Schulz WA. Glutathione transferase isoenzyme genotypes in patients with prostate and bladder carcinoma. Arch Toxicol 2000;74:521-6. [PubMed] [CrossRef]

  • Andonova IE, Sarueva RB, Horvath AD, Simeonov VA, Dimitrov PS, Petropoulos EA, Ganev lkan VS. Endemic nephropathy and genetic variants of glutathione Stransferases. J Nephrol 2004;17:390-8.

  • Lash LH, Andrews MW. Cytotoxicity of S-(1,2-dichlorovinyl) glutathione and S-(1,2dichlorovinyl)-L-cysteine in isolated rat kidney cells. J Biol Chem 1986;261:13076-81.

  • van Bladeren PJ. Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 2000;129:61-76. [PubMed] [CrossRef]

  • Pfohl-Leszkowicz A, Bartsch H, Azemar B, Mohr U, Esteve J, Castegnaro M. MESNA protects rats against nephrotoxicity but not carcinogenicity induced by ochratoxin A, implicating two separate pathways. Facta Universitatis, Ser Med Biol 2002;9:57-63.

  • Faucet-Marquis V, Pont F, Størmer F, Rizk T, Castegnaro M, Pfohl-Leszkowicz A. Evidence of a new dechlorinated OTA derivative formed in opossum kidney cell cultures after pre-treatment by modulators of glutathione pathways. Correlation with DNA adducts formation. Mol Nutr Food Res 2006;50:531-42.

  • Hartge P, Hoover R, West DW, Lyon JL. Coffee drinking and risk of bladder cancer. J Natl Cancer Inst 1983;70:1021-6. [PubMed]

  • Lebrun S, Golka K, Schulze H, Follman W. Glutathione S-transferase polymorphisms and ochratoxin A toxicity in primary human urothelial cells. Toxicology 2006;224:81-90. [CrossRef] [PubMed]

  • Ringot D, Chango A, Schneider YJ, Larondelle Y. Toxicokinetics and toxicodynamics of ochratoxin A, an update. Chem Biol Interact 2006;159:18-46. [CrossRef] [PubMed]

  • Kurashi N, Inoue M, Iwasaki S, Sasazuki S, Tsugane S. Coffee, green tea and caffeine consumption and subsequent risk of bladder cancer in relation to smoking status: a prospective study in Japan. Cancer Sci 2009;100:284-91. [CrossRef]

  • Covolo L, Placide D, Gelatti U, Carta A, Di Carlo AS, Lodetti P, Picciche A, Orizi G, Campagna M, Arici C, Dorru S. Bladder cancer, GSTs, NAT1, NAT2, sult 1A1, XRRC1, XRRC3, XPD genetic polymorphisms and coffee consumption: a case control study. Eur J Epidemiol 2008;23:355-62. [CrossRef]

  • Pfohl-Leszkowicz A, Petkova-Bocharova T, Chernozemsky IN, Castegnaro M. Balkan endemic nephropathy and associated urinary tract tumours: a review on aetiological causes and the potential role of mycotoxins. Food Addit Contam 2002;19:282-302. [CrossRef]

  • Mayer S, Curtui V, Usleber E, Gareis M. Airborne mycotoxins in dust of grain elevators. Mycotoxin Res 2007;23:94-100. [CrossRef] [PubMed]

  • Nguyen MT, Tozlovanu M, Tran TL, Pfohl-Leszkowicz A. Occurrence of aflatoxin B1, citrinin and ochratoxin A in rice in five provinces of the central region of Vietnam. Food Chem 2007;105:42-7. [CrossRef]

  • Levi CP, Trenk HL, Mohr HK. Study of the occurrence of ochratoxin A in green coffee beans. J Assoc Off Anal Chem 1974;57:866-70. [PubMed]

  • Blanc M, Pittet A, Munoz-Box R, Viani R. Behavior of ochratoxin A during green coffee roasting and soluble coffee manufacture. J Agric Food Chem 1998;46:673-5. [PubMed] [CrossRef]

  • International Coffee Organization (ICO). OTA risk management: guidelines for green coffee buying [displayed 12 November 2009]. Available at http://www.ico.org/documents/ed1939e.pdf

  • Domijan A-M, Peraica M, Jurjević Z, Ivić D, Cvjetković B. Fumonisin B1, fumonisin B2, zearalenone and ochratoxin A contamination of maize in Croatia. Food Addit Contam 2005;22:677-80. [CrossRef] [PubMed]

  • Jurjević L, Solfrizzo M, Cvjetković B, de Girolamo A, Visconti A. Ocurrence of beauvericin in corn from Croatia. Food Technol Biotechnol 2002;40:91-4.

  • Vrabcheva T, Usleber E, Dietrich R, Märtlbauer E. Cooccurrence of ochratoxin A and citrinin in cereals from Bulgarian villages with a history of Balkan endemic nephropathy. J Agric Food Chem 2000;48:2483-8. [CrossRef]

  • Petkova-Bocharova T, Castegnaro M, Michelon J, Maru V. Ochratoxin A and other mycotoxins in cereals from an area of Balkan endemic nephropathy and urinary tract tumours in Bulgaria. In: Bartsch H, Dirheimer G, Categnaro M, Pleština R, Chernozemsky IN, editors. Mycotoxins, endemic nephropathy and urinary tract tumours. IARC Scientific Publication 115. Lyon: IARC; 1991. p. 83-7.

  • Petkova-Bocharova T, Castegnaro M, Pfohl-Leszkowicz A, Garren L, Grosso F, Nikolov I, Vrabcheva T, Dragacci S, Chernozemsky I. Analysis of ochratoxin A in serum and urine of inhabitants from an area with Balkan Endemic Nephropathy: A one month follow up study. Facta Universitatis, Ser Med Biol 2003;10:62-8.

  • Di Paolo N, Guarinieri A, Loi F, Sacchi G, Mangiarotti AM, Di Paolo M. Acute renal failure from inhalation of mycotoxins. Nephron 1993;64:621-5. [CrossRef] [PubMed]

  • Skaug MA, Helland I, Solvoll K, Saugstad OD. Presence of ochratoxin A in human milk in relation to dietary intake. Food Addit Contam 2001;18:321-7. [PubMed]

  • Skaug MA, Eduard W, Størmer FC. Ochratoxin in airborne dust and fungal conidia. Mycopathologia 2001;151:93-8. [CrossRef] [PubMed]

  • Brera C, Caputi R, Miraglia M, Iavicoli I, Salerno A, Carelli G. Exposure assessment to mycotoxins in workplaces: aflatoxins and ochratoxin A occurrence in airborne dusts and human sera. Microchem J 2002;73:167-73. [CrossRef]

  • Iavicoli I, Brera C, Carelli G, Caputi RM, Marinaccio A, Miraglia M. External and internal dose in subjects occupationally exposed to ochratoxin A. Int Arch Occup Environ Health 2002;75:381-6. [PubMed] [CrossRef]

  • Gareis M, Meussdoerffer F. Dust of grains and malts as a source of ochratoxin A exposure. Mycotoxin Res 2000;16:127-30. [PubMed] [CrossRef]

  • Wang Y, Chai T, Lu G, Quan C, Duan H, Yao M, Zucker B-A, Schlenker G. Simultaneous detection of airborne aflatoxin, ochratoxin and zearalenone in a poultry house by immunoaffinity clean-up and high-performance liquid chromatography. Environ Res 2008; 107 139-44.

  • Abramson D, Hulasare R, White NDG, Jayas DS, Marquadt RR. Mycotoxin formation in hullness barley during granary storage at 15% and 19% moisture content. J Stored Prod Res 1999;35:297-305.

  • Chandelier A, Michelet JY, Tangni EK, Baert K, Moons E, Vinkx C. Mycotoxins survey in Belgium and toxigenic Fusarium in Belgian wheat. In: Logrieco A, Visconti A, editors. An overview on toxinogenic fungi and mycotoxins in Europe. Amsterdam: Kluwer Academic Publishers; 2004. p. 11-32.

  • Tangni EK, Pussemier L. Ochratoxin A and citrinin loads in stored wheat grains: impact of grain dust and possible prediction using ergosterol measurement. Food Addit Contam, 2006;23:181-9. [PubMed] [CrossRef]

  • Pussemier L, Larondelle Y, van Peteghen C, Huyghebaert A. Chemical safety of conventionally and organically produced foodstuffs: A tentative comparison under Belgian conditions. Food Control 2006;17:14-21. [CrossRef]

  • Dacarro C, Grisoli P, del Frate G, Villani S, Grignani E, Cottica D. Micro-organisms and dust exposure in an OItalian grain mill. J Appl Microbiol 2005;98:163-71. [CrossRef]

  • Halstensen AS, Nordby KC, Klemsdal SS, Elen O, Eduard W. Ochratoxin A in grain dust: estimated exposure and relations to agricultural practices in grain production. Ann Agric Environ Med 2004;11:245-54. [PubMed]

  • Macgeorge KM, Mantle PG. Nephrotoxicity of Penicillium aurantiogriseum and P. commune from an endemic area of Yugoslavia. Mycopathologia 1990;112:139-45. [CrossRef]

  • Pereira VJ, Basílio MC, Fernandes D, Domingues M, Paiva JM, Benoliel MJ, Crespo MT, San Romão MV. Occurrence of filamentous fungi and yeasts in three different drinking water sources. Water Res 2009;43:3813-9. [PubMed] [CrossRef]

  • Paterson RRM, Kelley J, Gallagher M. Natural occurrence of aflatoxins and Aspergillus flavus (link) in water. Lett App Microbiol 1997;25:435-6. [CrossRef]

  • Kuiper-Goodman T, Richard I, Kiparissis Y. Trends in exposure to ochratoxin A suggest a plausible role for this mycotoxin in the development of Balkan endemic nephropathy. In: Proceeding of the workshop "Recent advances in Balkan endemic nephropathy research"; 16-18 April 2009. Belgrade: Serbian Academy of Sciences and Arts; 2009.

  • Walker R. Mycotoxins of growing interest. Third joint FAO/WHO/UNEP International Conference on Mycotoxins, Tunis 1999 [displayed 12 November 2009]. Available at ftp://ftp.fao.org/es/esn/food/myco5b.pdf

  • Kuiper-Goodman T, Scott PM. Risk assessment of the mycotoxin ochratoxin A. Biomed Environ Sci 1989;2:179-248.

  • Manderville RA. Ambident reactivity of phenoxyl radicals in DNA adduction. Can J Chem 2005;83:1261-7. [CrossRef]

  • Scott PM, Kanhere SR, Lau BP, Lewis DA, Hayward S, Ryan JJ, Kuiper-Goodman T. Survey of Canadian human blood plasma for ochratoxin A. Food Addit Contam 1998;5:555-62. [CrossRef]

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