Enzymes metabolizing aristolochic acid and their contribution to the development of aristolochic acid nephropathy and urothelial cancer

Current Drug Metabolism

Volumn 14, Issue 6, 2013, Pages 695-705

  Stiborová, Marie ^a   Martínek, Václav ^a   Frei, Eva ^b   Arlt, Volker M ^c   Schmeiser, Heinz H ^b  

^a CHARLES UNIVERSITY   (Czech Republic)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Aristolochic acid; Aristolochic acid nephropathy; Balkan endemic nephropathy; Cytochromes P450 1A1 and 1A2; Metabolic activation and detoxication; biotransformation enzymes; NAD(P)H:quinone oxidoreductase

Indexed keywords

ACYLTRANSFERASE; ARISTOLOCHIC ACID; ARISTOLOCHIC ACID I; ARISTOLOLACTAM; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; DNA; DRUG METABOLITE; GLUCURONOSYLTRANSFERASE; O DEMETHYLASE; OXIDOREDUCTASE; PROSTAGLANDIN SYNTHASE; PROTEIN P53; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE (PHOSPHATE) DEHYDROGENASE (QUINONE); REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SULFOTRANSFERASE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CARCINOGENESIS; DNA ADDUCT; DNA BINDING; DRUG METABOLISM; GENETIC POLYMORPHISM; HUMAN; IN VITRO STUDY; IN VIVO STUDY; KIDNEY DISEASE; KIDNEY INJURY; LIVER MICROSOME; METABOLIC ACTIVATION; METABOLITE; MOLECULAR MODEL; NONHUMAN; REDUCTION; RISK; URINARY TRACT; UROGENITAL TRACT CANCER;

ANIMALS; ARISTOLOCHIC ACIDS; HUMANS; KIDNEY DISEASES; NEOPLASMS, GLANDULAR AND EPITHELIAL; OXIDOREDUCTASES; UROTHELIUM;

EID: 84882303544     PISSN: 13892002     EISSN: 18755453     Source Type: Journal    
DOI: 10.2174/1389200211314060006     Document Type: Article

References (134)

1. IARC (International Agency for Research on Cancer). Some traditional herbal medicines, some mycotoxins, naphthalene and sty-rene. IARC Monogr. Eval. Carcinog. Risks Hum. 2002, 82, 1-556.
2. Debelle, F.D.; Vanherweghem, J.L.; Nortier, J.L. Aristolochic acid nephropathy: a worldwide problem. Kidney Int., 2008, 74(2), 158-169.
3. Schmeiser, H.H., Stiborová, M.; Arlt, V.M. Chemical and molecular basis of the carcinogenicity of Aristolochia plants. Curr. Opin. Drug Discov. Devel., 2009, 12(1), 141-148.
4. Vanherweghem, J.L.; Depierreux, M.; Tielemans, C.; Abramowicz, D.; Dratwa, M.; Jadoul, M.; Richard, C.; Valdervelde, D.; Ver-beelen, D.; Vanhaelen-Fastre, B.; Vanhaelen, M. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet, 1993, 341(8842), 387-391.
5. Nortier, J.L.; Martinez, M.C.; Schmeiser, H.H.; Arlt, V.M.; Bieler, C.A.; Perrin, M.; Depierreux, M.F.; De Pauw, L.; Abramowicz, D.; Vereerstraeten, P;, Vanherweghem, J.L. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). N. Engl. J. Med., 2000, 342(23), 1686-1692.
6. Arlt, V.M.; Stiborova, M.; Schmeiser, H.H. Aristolochic acid as a probable human cancer hazard in herbal remedies: a review. Mutagenesis, 2002, 17(4), 265-277.
7. Arlt, V.M.; Alunni-Perret, M.; Quatrehomme, G.; Ohayon, P.; Albano, L.; Gaid, H.; Michiels, J.F.; Meyrier, A.; Cassuto, E.; Wi-essler, M.; Schmeiser, H.H.; Cosyns, J.-P. Aristolochic acid (AA)-DNA adduct as marker of AA exposure and risk factor for AA nephropathy-associated cancer. Int. J. Cancer, 2004, 111(6), 977-980.
8. Lemy, A.; Wissing, K.M.; Rorive, S.; Zlotta, A.; Roumeguere, T.; Muniz Martinez, M.C.; Decaestecker, C.; Salmon, I.; Abramowicz, D.; Vanherweghem, J.L.; Nortier, J. Late onset of bladder urothe-lial carcinoma after kidney transplantation for end-stage aristolo-chic acid nephropathy: a case series with 15-year follow-up. Am. J. Kidney Dis., 2008, 51(3), 471-477.
9. Grosse, Y.; Baan, R.; Straif, K.; Secretan, B.; El Ghissassi, F.; Bouvard, V.; Benbrahim-Tallaa, L.; Guha, N.; Galichet, L.; Cogliano, V. A review of human carcinogens-Part A: pharmaceuticals. Lancet Oncol., 2009, 10(1), 13-14.
10. NTP (National Toxicology Program), Aristolochic Acids. Report on Carcinogens, Twelfth Edition, 2011, 45-49.
11. Arlt, V.M.; Ferluga, D.; Stiborova, M.; Pfohl-Leszkowicz, A.; Vukelic, M.; Vdovic, S.; Schmeiser, H.H.; Cosyns J.P. Is aristolo-chic acid a risk factor for Balkan endemic nephropathy-associated urothelial cancer? Int. J. Cancer, 2002, 101(5), 500-502.
12. Grollman, A.P.; 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, R.; Goodenough, A.K.; Rieger, R.; Vukelic, M.; Jelakovic, B. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc. Natl. Acad. Sci. U.S.A., 2007, 104(29), 12129-12134.
13. Nedelko, T.; Arlt, V.M.; Phillips, D.H.; Hollstein, M. TP53 mutation signature supports involvement of aristolochic acid in the aetiology of endemic nephropathy-associated tumours. Int. J. Cancer, 2009, 124(4), 987-990.
14. Jelakovic, B.; Karanovic, S.; Vukovic-Lela, I.; Miller, F.; Edwards, K.L.; Nikolic, J.; Tomic, K.; Slade, N.; Brdar, B.; Turesky, R.J.; Stipancic, Z.; Dittrich, D.; Grollman, A.P.; Dickman, K.G. Aristolactam-DNA adducts are a biomarker of environmental exposure to aristolochic acid. Kidney Int., 2012, 81(6), 559-567.
15. Ivic, M. Etiology of endemic nephropathy. Lijec Vjesn., 1969, 91(12), 1273-1281.
16. Hranjec, T.; Kovac, A.; Kos, J.; Mao, W.; Chen, J.J.; Grollman, A.P.; Jelakovic, B. Endemic nephropathy: the case for chronic poisoning by aristolochia. Croat. Med. J., 2005, 46(1), 116-125.
17. Schmeiser, H.H.; Kucab, J.E.; Arlt, V.M.; Phillips, D.H.; Hollstein, M.; Gluhovschi, G.; Gluhovschi, C.; Modilca, M.; Daminescu, L.; Petrica, L.; Velciov, S. Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania. Environ. Mol. Mutagen., 2012, 53(8), 636-641.
18. Shibutani, S.; Dong, H.; Suzuki, N.; Ueda, S.; Miller, F.; Grollman, A.P. Selective toxicity of aristolochic acids I and II. Drug Metab. Dispos., 2007, 35(7), 1217-1222.
19. Depierreux, M.; Van Damme, B.; Vanden Houte, K.; Vanher-weghem, J.L. Pathologic aspects of a newly described nephropathy related to the prolonged use of Chinese herbs. Am. J. Kidney Dis., 1994, 24(2), 172-180.
20. Yang, L.; Li, X.; Wang, H. Possible mechanisms explaining the tendency towards interstitial fibrosis in aristolochic acid-induced acute tubular necrosis. Nephrol. Dial. Transplant., 2007, 22(2), 445-456.
21. Yang, L.; Su, T.; Li, X.M.; Wang, X.; Cai, S.Q.; Meng, L.Q.; Zou, W.Z.; Wang, H.Y. Aristolochic acid nephropathy: variation in presentation and prognosis. Nephrol. Dial. Transplant., 2012, 27(1), 292-298.
22. Sato, N.; Takahashi, D.; Chen, S.M,; Tsuchiya, R.; Mukoyama, T.; Yamagata, S.; Ogawa, M.; Yoshida, M.; Kondo, S.; Satoh, N.; Ueda, S. Acute nephrotoxicity of aristolochic acids in mice. J. Pharm. Pharmacol., 2004, 56(2), 221-229.
23. Bakhiya, N.; Arlt, V.M.; Bahn, A.; Burckhardt, G.; Phillips, D.H.; Glatt, H. Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy. Toxicology, 2009, 264(1-2), 74-79.
24. Baudoux, T.E.; Pozdzik, A.A.; Arlt, V.M.; De Prez, E.G.; Antoine, M.H.; Quellard, N.; Goujon. J.M.; Nortier, J.L. Probenecid prevents acute tubular necrosis in a mouse model of aristolochic acid nephropathy. Kidney Int., 2012, 82(10), 1105-1113.
25. Xue, X.; Gong, L.K.; Maeda, K.; Luan, Y.; Qi, X.M.; Sugiyama, Y.; Ren, J. Critical role of organic anion transporters 1 and 3 in kidney accumulation and toxicity of aristolochic acid I. Mol. Pharm., 2011, 8(6), 2183-2192
26. Nortier, J.L.; Schmeiser, H.H.; Martinez, M.C.M.; Arlt, V.M.; Vervaet, C; Garbar, C.H.; Daelemans, P.; Vanherweghem, J.L. Invasive urothelial carcinoma after exposure to Chinese herbal medicine containing aristolochic acid may occur without severe renal failure. Nephrol. Dial. Transplant., 2003, 18(2), 426-428.
27. Qi, X.; Cai, Y.; Gong, L.; Liu, L.; Chen, F.; Xiao, Y.; Wu, X.; Li, Y.; Xue, X.; Ren, J. Role of mitochondrial permeability transition in human renal tubuar epithelial cell death induced by aristolochic acid. Toxicol. Appl. Pharmacol, 2007, 222(1), 105-110.
28. Romanov, V.; Whyard, T.; Bonala, R.; Johnson, F.; Grollman, A. Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in renal tubular epithelial cells. Apoptosis, 2011, 16(12), 1217-1228.
29. Zhu, S.; Wang, Y.; Jin, J.; Guan, C; Li, M.; Xi, C; Ouyang, Z.; Chen, M.; Qiu, Y.; Huang, M.; Huang, Z. Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells. Toxicol. In Vitro, 2012, 26(5), 663-671.
30. Zhou, L.; Fu, P.; Huang, X.R.; Liu, F.; Lai, K.N.; Lan, H.Y. Activation of p53 promotesrenal injury in acute aristolochic acid nephropathy. J. Am. Soc. Nephrol, 2010, 21(1), 31-41
31. Rui, H.L.; Wang, Y.Y.; Cheng, H.; Chen, Y.P. JNK-dependent AP-1 activation is required for aristolochic acid-induced TGF-p1 synthesis in human renal proximal epithelial cells. Am. J. Physiol. Re-nal Physiol., 2012, 302(12), F1569-F1575.
32. Zeng, Y.; Yang, X.; Wang, J.; Fan, J.; Kong, Q.; Yu, X. Aristolochic acid I induced autophagy extenuates cell apoptosis via ERK 1/2 pathway in renal tubular epithelial cells. PLoS One, 2012, 7(1), e30312.
33. Arlt, V.M.; Stiborová, M.; vom Brocke, J; Simoes, M.L.; Lord, G.M.; Nortier, J.L.; Hollstein, M.; Phillips, D.H.; Schmeiser, H.H. Aristolochic acid mutagenesis: molecular clues to the etiology of Balkan endemic nephropathy-associated urothelial cancer. Carcinogenesis, 2007, 28(11), 2253-2261.
34. Stiborová, M.; Frei, E.; Arlt, V, M,; Schmeiser, H.H. Metabolic activation of carcinogenic aristolochic acid, a risk factor for Balkan endemic nephropathy. Mutat. Res., 2008, 658(12), 55-67.
35. Schmeiser, H.H.; Bieler, C.A.; Wiessler, M.; van Ypersele de Stri-hou, C; Cosyns, J.P. Detection of DNA adducts formed by aristolochic acid in renal tissue from patients with Chinese herbs nephropathy. Cancer Res. 1996, 56(9), 2025-2028.
36. Lord, G.M.; Cook, T.; Arlt, V.M.; Schmeiser, H.H.; Williams, G.; Pusey, CD. Urothelial malignant disease and Chinese herbal nephropathy. Lancet, 2001, 358(9292), 1515-1516.
37. Yun, B.H.; Rosenquist, T.A.; Sidorenko, V.; Iden, C.R.; Chen, C.H.; Pu, Y.S.; Bonala, R.; Johnson, F.; Dickman, K.G.; Grollman, A.P.; Turesky, R.J. Biomonitoring of aristolactam-DNA adducts in human tissues using ultra-performance liquid chromatography/ion-trap mass spectrometry. Chem. Res. Toxicol, 2012, 25(5), 1119-1131.
38. Broschard, T.H.; Wiessler, M.; von der Lieth, C.W.; Schmeiser, H.H. Translesional synthesis on DNA templates containing site-specifically placed deoxyadenosine and deoxyguanosine adducts formed by the plant carcinogen aristolochic acid. Carcinogenesis, 1994, 15(10), 2331-2340.
39. Chen, T.; Guo, L.; Zhang, L.; Shi, L.; Fang, H.; Sun, Y.; Fuscoe, J.C.; Mei, N. Gene expression profiles distinguish the carcinogenic effects of aristolochic acid in target (kidney) and non-target (liver) tissues in rats. BMC Bioinformatics, 2006, 7(Suppl 2), S20.
40. Kohara, A.; Suzuki, T.; Honma, M.; Ohwada, T.; Hayashi, M. Mutagenicity of aristolochic acid in the lambda/lacZ transgenic mouse (MutaMouse). Mutat. Res., 2002, 515(1-2), 63-72.
41. McDaniel, L.P.; Elander, E.R.; Guo, X.; Chen, T.; Arlt, V.M.; Mei, N. Mutagenicity and DNA adduct formation by aristolochic acid in the spleen of Big Blue® rats. Environ. Mol. Mutagen., 2012, 53(5), 358-368.
42. Mei, N.; Arlt, V.M.; Phillips, D.H.; Heflich, R.H.; Chen, T. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver. Mutat. Res., 2006, 602(1-2), 83-91.
43. Xing, G.; Qi, X.; Chen, M.; Wu, Y.; Yao, J.; Gong, L.; Nohmi, T.; Luan, Y.; Ren, J. Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney. Mutat. Res., 2012, 743(1-2), 52-58.
44. Schmeiser, H.H.; Janssen, W.; Lyons, J.; Scherf, H.R.; Pfau, W.; Buchmann, A.; Bartram, M.; Wiessler, C.R. Aristolochic acid activates ras genes in rat tumors at deoxyadenosine residues, Cancer Res., 1990, 50(17), 5464-5469.
45. Wang, Y.; Meng, F.; Arlt, V.M.; Mei, N.; Chen, T.; Parsons, B.L. Aristolochic acid-induced carcinogenesis examined by ACB-PCR quantification of H-Ras and K-Ras mutant fraction. Mutagenesis, 2011, 26(5), 619-628
46. Wang, Y.; Arlt, V.M.; Roufosse, C.A.; McKim, K.L.; Myers, M.B.; Phillips, D.H.; Parsons, B.L. ACB-PCR measurement of H-ras codon 61 CAA-CTA mutation provides an early indication of aristolochic acid I carcinogenic effect in tumor target tissues. Environ. Mol. Mutagen., 2012, 53(7), 495-504.
47. Arlt, V.M.; Wiessler, M.; Schmeiser, H.H. Using polymerase arrest to detect DNA binding specificity of aristolochic acid in the mouse H-ras gene. Carcinogenesis, 2000, 21(2), 235-242.
48. Lord, G.M.; Hollstein, M.; Arlt, V.M.; Roufosse, C; Pusey, CD.; Cook, T.; Schmeiser, H.H. DNA adducts and p53 mutations in a patient with aristolochic acid-associated nephropathy. Am. J. Kidney Dis., 2004, 43(4), e11-17.
49. Moriya, M.; Slade, N.; Brdar, B.; Medverec, Z.; Tomic, K.; Jelakovic, B.; Wu, L.; Truong, S.; Fernandes, A.; Grollman, A.P. TP53 Mutational signature for aristolochic acid: an environmental carcinogen. Int. J. Cancer, 2011, 129(6), 1532-1536.
50. Feldmeyer, N.; Schmeiser, H.H.; Muehlbauer, K.R.; Belharazem, D.; Knyazev, Y.; Nedelko, T.; Hollstein, M. Further studies with a cell immortalization assay to investigate the mutation signature of aristolochic acid in human p53 sequences. Mutat. Res., 2006, 608(2), 163-168.
51. Liu, Z.; Hergenhahn, M.; Schmeiser, H.H.; Wogan, G.N.; Hong, A.; Hollstein, M. Human tumor p53 mutations are selected for in mouse embryonic fibroblasts harboring a humanized p53 gene. Proc. Natl. Acad. Sci. U. S. A., 2004, 101(9), 2963-2968.
52. Arlt, V.M.; Schmeiser, H.H.; Pfeifer, G.P. Sequence-specific detection of aristolochic acid-DNA adducts in the human p53 gene by terminal transferase-dependent PCR. Carcinogenesis, 2001, 22(1), 133-140.
53. Kucab, J.E.; Phillips, D.H.; Arlt, V.M. Linking environmental carcinogen exposure to TP53 mutations in human tumours using the human TP53 knock-in (Hupki) mouse model. FEBS J., 2010, 277(12), 2567-2583.
54. Chen, C.H.; Dickman, K.G.; Moriya, M.; Zavadil, J.; Sidorenko, V.S.; Edwards, K.L.; Gnatenko, D.V.; Wu, L.; Turesky, R.J.; Wu, X.R.; Pu, Y.S.; Grollman, A.P. Aristolochic acid-associated urothelial cancer in Taiwan. Proc. Natl. Acad. Sci. U.S.A., 2012, 109(21), 8241-8246.
55. Olivier, M.; Hollstein, M.; Schmeiser, H.H.; Straif, K.; Wild, C.P. Upper urinary tract urothelial cancers: where it is A:T. Nat. Rev. Cancer, 2012, 12(8), 503-504.
56. Arlt, V.M.; Zuo, J.; Trenz, K.; Roufosse, C.A.; Lord, G.M.; Nortier, J.L.; Schmeiser, H.H.; Hollstein, M.; Phillips, D.H. Gene expression changes induced by the human carcinogen aristolochic acid I in renal and hepatic tissue of mice. Int. J. Cancer, 2011, 128(1), 21-32.
57. Simões, M.L.; Hockley, S.L.; Schwerdtle, T.; da Costa, G.G.; Schmeiser, H.H.; Phillips, D.H.; Arlt, V.M. Gene expression profiles modulated by the human carcinogen aristolochic acid I in human cancer cells and their dependence on TP53. Toxicol. Appl. Pharmacol, 2008, 232(1), 86-98
58. Stemmer, K.; Ellinger-Ziegelbauer, H.; Ahr, H.J.; Dietrich, D.R. Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis. Cancer Res., 2007, 67(9), 4052-4068.
59. Stemmer, K.; Ellinger-Ziegelbauer, H.; Ahr, H.J.; Dietrich, D.R. Molecular characterization of preneoplastic lesions provides insight on the development of renal tumors. Am. J. Pathol, 2009, 175(4), 1686-1698.
60. Mix, D.B.; Guinaudeau, H.; Shamma, M. The aristolochic acids and aristolactams. J. Nat. Products, 1982, 45(4), 657-666.
61. Krumbiegel, G.; Hallensleben, J.; Mennicke, W.H.; Rittmann, N. Studies on the metabolism of aristolochic acids I and II. Xenobi-otica, 1987, 17(8), 981-991.
62. Chan, W.; Cu, L.; Xu, G.; Cai, Z. Study of the phase I and phase II metabolism of nephrotoxin aristolochic acid by liquid chromatog-raphy/tandem mass spectrometry. Rapid. Commun. Mass Spec-trom., 2006, 20(11), 1755-1760.
63. Chan, W.; Luo, H.-B.; Zheng, Y.; Cheng, Y.-K.; Cai Z. Investigation of the metabolism and reductive activation of carcinogenic aristolochic acid in rats. Drug Metab. Dispos., 2007, 35(6), 866-874.
64. Shibutani, S.; Bonala, R.R.; Rosenquist, T.; Rieger, R.; Suzuki, N.; Johnson, F.; Miller, F.; Grollman, A.P. Detoxification of aristolochic acid I by O-demethylation: less nephrotoxicity and genotoxic-ity of aristolochic acid Ia in rodents. Int. J. Cancer, 2010, 127(5):1021-1027.
65. Schmeiser, H.H.; Pool, B.L.; Wiessler, M. Identification and mutagenicity of metabolites of aristolochic acid formed by rat liver. Carcinogenesis, 1986, 7(1) 59-63.
66. Maier, P.; Schawalder, H.; Weibel, B. Low oxygen tension as found in tissues in vivo, alters the mutagenic activity of aristolochic acid I and II. Environ. Mol. Mutagen., 1987, 10(3), 275-284.
67. Priestap, H.A.; Torres, M.C.; Rieger, R.A.; Dickman, K.G.; Freshwater, T.; Taft, D.R.; Barbieri, M.A.; Iden, C.R. Aristolochic acid I metabolism in the isolated perfused rat kidney. Chem. Res. Toxicol, 2012, 25(1), 130-139.
68. Cosyns, J.P. Aristolochic acid and "Chinese herbs nephropathy": a review of the evidence to date. Drug Safety, 2003, 26(1), 33-48.
69. Stiborová, M.; Frei, E.; Schmeiser, H.H. Biotransformation enzymes in development of renal injury and urothelial cancer caused by aristolochic acid. Kidney Int., 2008, 73(11), 1209-1211.
70. Stiborová, M.; Frei, E.; Arlt, V.M.; Schmeiser, H.H. The role of biotransformation enzymes in the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions and difficult answers. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2009, 153(1), 5-11.
71. Slade, N.; Moll, U.M.; Brdar, B.; Zoric, A.; Jelakovic, B. p53 mutations as fingerprints for aristolochic acid: an environmental carcinogen in endemic (Balkan) nephropathy. Mutat. Res., 2009, 663(1-2), 1-8.
72. 32P-postlabeling/polyacrylamide gel electrophoresis analysis. Drug Metab. Dispos., 2006, 34(7), 1122-1127.
73. Stiborová, M.; Frei, E.; Schmeiser, H.H.; Wiessler, M. Cytochrome P-450 and peroxidase oxidize detoxication products of carcinoge-neic aristolochic acids (aristolactams) to reactive metabolites binding to DNA in vitro. Collect. Czech. Chem. Commun., 1995, 60(12), 2189-2199.
74. Stiborová, M.; Frei, E.; Breuer, A.; Bieler, C.A.; Schmeiser, H.H. Aristolactam I a metabolite of aristolochic acid I upon activation forms an adduct found in DNA of patients with Chinese herbs nephropathy. Exp. Toxic. Pathol, 1999, 51(45), 421-427.
75. Eling, T.E.; Thompson, D.C.; Foureman, G.L.; Curtis, J.F.; Hughes, M.F. Prostaglandin H synthase and xenobiotic oxidation, Annu. Rev. Pharmacol. Toxicol, 1990, 30, 1-45.
76. Eling, T.E.; Curtis, J.F. Xenobiotic metabolism by prostaglandin H synthase. Pharm. Ther., 1992, 53(2), 261-273.
77. Li, J.; Zhang, L.; Jiang, Z.; Shu, B.; Li, F.; Bao, Q.; Zhang, L. Toxicities of aristolochic acid I and aristololactam I in cultured renal epithelial cells. Toxicol. In Vitro, 2010, 24(4), 1092-1097.
78. Martinez, M.C.; Nortier, J.; Vereerstaeten, P.; Vanherweghem, J.L. Progression rate of Chinese herb nephropathy: impact of Aristolo-chia fangchi ingested dose. Nephrol. Dial. Transplant., 2002, 17(11), 408-412.
79. Smith, G.; Stanley, L.A.; Sim, E.R. Wolf, C.R. Metabolic polymorphism and cancer susceptibility. Cancer Surveys, 1995, 25, 27-65.
80. Toncheva, D.I.; von Ahsen, N.; Atanasova, S.Y.; Dimitrov, T.G.; Armstrong, V.M.; Oellerich, M. Identification of NQO1 and GSTs genotype frequencies in Bulgarian patients with Balkan endemic nephropathy. J. Nephrol, 2004, 17(3), 384-389.
81. Toncheva, D. Genetic studies in BEN and associated urothelial cancers. Coll. Antropol, 2006, 30(Suppl 1), 34.
82. Atanasova, S.Y.; von Ahsen, N.; Toncheva, D.I.; Dimitrov, T.G.; Oellerich, M.; Amstrong, V.M. Genetic polymorphism of cytochrome P450 among patients with Balkan endemic nephropathy (BEN). Clin. Biochem., 2005, 38(3) 223-228.
83. Chen, B.; Bai, Y.; Sun, M.; Ni, X.; Yang, Y.; Yang, Y.; Zheng, S.; Xu, F.; Dai, S. Glutathione S-transferases T1 null genotype is associated with susceptibility to aristolochic acid nephropathy. Int. Urol. Nephrol, 2012, 44(1), 301-307.
84. Stiborová, M.; Frei, E.; Sopko, B.; Wiessler, M.; Schmeiser, H.H. Carcinogenic aristolochic acids upon activation by DT-diaphorase form adducts found in DNA of patients with Chinese herbs nephropathy. Carcinogenesis, 2002, 23(4), 617-625.
85. Stiborová, M.; Frei, E.; Sopko, B.; Sopková, K.; Marková, V.; Lanková, M.; Kumstyfová, T.; Wiessler, M.; Schmeiser, H.H. Human cytosolic enzymes involved in the metabolic activation of carcinogenic aristolochic acid: evidence for reductive activation by human NAD(P)H:quinone oxidoreductase. Carcinogenesis, 2003, 24(10), 1695-1703.
86. Stiborová, M.; Mares, J.; Frei, E.; Arlt, V.M.; Martínek, V.; Schmeiser, H.H. The human carcinogen aristolochic acid i is activated to form DNA adducts by human NAD(P)H:quinone oxidoreductase without the contribution of acetyltransferases or sul-fotransferases. Environ. Mol. Mutagen., 2011, 52(6), 448-459.
87. Stiborová, M.; Hájek, M.; Vosmiková, H.; Frei, E.; Schmeiser, H.H. Isolation of DT-diaphorase [NAD(P)H dehydrogenase (qui-none)] from rat liver cytosol: identification of new substrates, carcinogenic aristolochic acids. Collect. Czech. Chem. Commun., 2001, 66(11), 959-972.
88. 32P-post-labelling: evidence for reductive activation by peroxidases. Carcinogenesis, 1997, 18(5), 1055-1062.
89. Martinek, V.; Kubickova, B.; Arlt, V.M.; Frei, E.; Schmeiser, H.H.; Hudecek, J.; Stiborova, M. Comparison of activation of aristolochic acid I and II with NADPH:quinone oxidoreductase, sulphotrans-ferases and N-acetyltranferases. Neuro Endocrinol Lett, 2011, 32(Suppl 1), 57-70.
90. Meinl, W.; Pabel, U.; Osterloh-Quitroz, H.; Hengstler, J.G.; Glatt, H. Human sulphotransferases are involved in the activation of aristolochic acids and are expressed in renal target tissue. Int. J. Cancer, 2006, 118(5), 1090-1097.
91. Levova, K.; Moserova, M.; Nebert, D.W.; Phillips, D.H.; Frei, E.; Schmeiser, H.H.; Arlt, V.M.; Stiborova, M. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I. Toxicol. Appl. Pharmacol, 2012, 265(3), 360-367 (2012).
92. Chen, M.; Gong, L.; Qi, X.; Xing, G.; Luan, Y.; Wu, Y.; Xiao, Y.; Yao, J.; Li, Y.; Xue, X.; Pan, G.; Ren, J. Inhibition of renal NQO1 activity by dicoumarol suppresses nitroreduction of aristolochic acid I and attenuates its nephrotoxicity. Toxicol. Sci., 2011, 122(2), 288-296.
93. Radjendirane, V.; Joseph, P.; Lee, Y. H.; Kimura, S.; Klein-Szanto, A. J.; Gonzalez, F. J.; Jaiswal, A. K. Disruption of the DT diaphorase (NQO1) gene in mice leads to increased menadione toxicity. J. Biol. Chem., 1998, 273(13), 7382-7389.
94. Stiborová, M.; Frei, E.; Wiessler, M.; Schmeiser, H.H. Human enzymes involved in the metabolic activation of carcinogenic aristolochic acids: evidence for reductive activation by cytochrome P450 1A1 and 1A2. Chem. Res. Toxicol, 2001, 14(8), 1128-1137.
95. Stiborová, M.; Frei, E.; Hodek, P.; Wiessler, M.; Schmeiser, H.H. Human hepatic and renal microsomes, cytochromes P450 1A1/2, NADPH:cytochrome P450 reductase and prostaglandin H synthase mediate the formation of aristolochic acid-DNA adducts found in patients with urothelial cancer. Int. J. Cancer, 2005, 113(2), 189-197.
96. Stiborová, M.; Sopko, B.; Hodek, P.; Frei, E.; Schmeiser, H.H.; Hudecek, J. The binding of aristolochic acid I to the active site of human cytochromes P450 1A1 and 1A2 explains their potential to reductively activate this human carcinogen. Cancer Lett, 2005, 229(2), 193-204.
97. Drahushuk, A.T.; McGarrigle, B.P.; Larsen, K.E.; Stegeman, J.J.; Olson, J.R. Detection of CYP1A1 protein in human liver and induction by TCDD in precision-cut liver slices incubated in dynamic organ culture. Carcinogenesis, 1998, 19(8), 1361-1368.
98. Stiborová, M.; Martínek, V.; Rydlová, H.; Hodek, P.; Frei, E. Sudan I is a potential carcinogen for humans: evidence for its metabolic activation and detoxication by human recombinant cytochrome P450 1A1 and liver microsomes, Cancer Res., 2002, 62(20) 5678-5684.
99. Dragin, N.; Uno, S.; Wang, B.; Dalton, T.P.; Nebert, D.W. Generation of 'humanized' hCYP1A1-1A2-Cyp1a1/1a2(-/-) mouse line. Biochem. Biophys. Res. Commun., 2007, 359(3), 635-642.
100. dmouse line harboring the poor-affinity aryl hydrocarbon receptor. Biochem. Biophys. Res. Commun., 2008, 376(4), 775-780.
101. Stiborová, M.; Levová, K.; Bárta F.; Shi, Z.; Frei, E.; Schmeiser, H.H.; Nebert, D.W.; Phillips, D.H.; Arlt, V.M. Bioactivation versus detoxication of the urothelial carcinogen aristolochic acid I by human cytochrome P450 1A1 and 1A2. Toxicol. Sci., 2012, 125(2), 345-358.
102. Jerabek, P.; Martinek, V.; Stiborova, M. Theoretical investigation of differences in nitroreduction of aristolochic acid I by cytochromes P450 1A1, 1A2 and 1B1. Neuro Endocrinol. Lett., 2012, 33(Suppl 3), 25-32.
103. Rendic, S.; DiCarlo, F.J. Human cytochrome P450 enzymes: A status report summarizing their reactions, substrates, inducers, and inhibitors, Drug Metab. Rev., 1997, 29(1-2) 413-480.
104. Levová, K.; Moserová, M.; Kotrbová, V.; Sulc, M.; Henderson, C.J.; Wolf, C.R.; Phillips, D.H.; Frei, E.; Schmeiser, H.H.; Mares, J.; Arlt, V.M.; Stiborová, M. Role of cytochromes P450 1A1/2 in detoxication and activation of carcinogenic aristolochic acid I: studies with the hepatic NADPH:cytochrome P450 reductase null (HRN) mouse model. Toxicol. Sci., 2011, 121(1), 43-56 (2011).
105. Stiborová, M.; Hájek, M.; Frei, E.; Schmeiser, H.H. Carcinogenic and nephrotoxic alkaloids aristolochic acids upon activation by NADPH:cytochrome P450 reductase form adducts found in DNA of patients with Chinese herbs nephropathy. Gen. Physiol. Biophys., 2001, 20(4), 375-392.
106. Gutierrez, A.; Grunau, A.; Paine, M.; Munro, A.W.; Wolf, C.R.; Roberts, G.C.; Scrutton, N.S. Electron transfer in human cytochrome P450 reductase. Biochem. Soc. Trans., 2003, 31(Pt 3), 497-501.
107. Hart, S.N.; Zhong, X.B. P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity. Expert Opin. Drug Metab. Toxicol., 2008, 4(4), 439-452.
108. Laursen, T.; Jensen, K.; Møller, B.L. Conformational changes of the NADPH-dependent cytochrome P450 reductase in the course of electron transfer to cytochromes P450. Biochim. Biophys. Acta, 2011, 1814(1), 132-138.
109. Iyanagi, T.; Xia, C; Kim, J.J. NADPH-cytochrome P450 oxidoreductase: Prototypic member of the diflavin reductase family. Arch. Biochem. Biophys., 2012, 528(1), 72-89.
110. 32P-postlabeling analysis of DNA adduct formation. Mutat. Res., 2001, 493(1-2), 149-160.
111. Arlt, V.M.; Levova, K.; Barta, F.; Shi, Z.; Evans, J.D.; Frei, E.; Schmeiser, H.H.; Nebert, D.W.; Phillips, D.H.; Stiborova, M. Role of P450 1A1 and P450 1A2 in bioactivation versus detoxication of the renal carcinogen aristolochic acid I: studies in Cyp1a1-/-, Cyp1a2-/-, and Cyp1a1/1a2-/-mice. Chem. Res. Toxicol., 2011, 24(10), 1710-1719.
112. Sístková, J.; Hudecek, J.; Hodek, P.; Frei, E.; Schmeiser, H.H.; Stiborová, M. Human cytochromes P450 1A1 and 1A2 participate in detoxication of carcinogenic aristolochic acid. Neuro Endocrinol. Lett., 2008, 29(5), 733-737.
113. Rosenquist, T.A.; Einolf, H.J.; Dickman, K.G.; Wang, L.; Smith, A.; Grollman, A.P. Cytochrome P450 1A2 detoxicates aristolochic acid in the mouse. Drug Metab. Disp., 2010, 38(5), 761-768.
114. Stiborova, M.; Mares, J.; Levova, K.; Pavlickova, J.; Barta F.; Hodek, P.; Frei, E.; Schmeiser, H.H. Role of cytochromes P450 in metabolism of carcinogenic aristolochic acid I: evidence of their contribution to aristolochic acid I detoxication and activation in rat liver. Neuro Endocrinol. Lett., 2011, 32(Suppl 1), 121-130.
115. 5. Pharmacol. Ther., 2003, 97(2), 139-152.
116. 5. Neuro Endocrinol. Lett., 2006, 27(Suppl. 2), 35-39.
117. 5 shifts oxidation of the anticancer drug ellipticine by cytochromes P450 1A1 and 1A2 from its detoxication to activation, thereby modulating its pharmacological efficacy. Biochem. Pharmacol., 2011, 82(6), 669-680.
118. Nebert, D.W. Comparison of gene expression in cell culture to that in the intact animal: Relevance to drugs and environmental toxicants. Focus on "development of a transactivator in hepatoma cells that allows expression of phase I, phase II, and chemical defense genes." Am. J. Physiol. Cell Physiol., 2006, 290(1), C37-C41.
119. Xiao, Y.; Ge, M.; Xue, X.; Wang, H.; Wu, X.; Li, L.; Liu, L.; Qi, X.; Zhang, Y.; Li, Y.; Xie, T.; Gu, J.; Ren, J. Detoxication role of hepatic cytochrome P450s in the kidney toxicity induced by aris-tolochic acid. Kidney Int., 2008, 73(11), 1231-1239.
120. Xue, X.; Xiao, Y.; Zhu, H.; Wang, H.; Liu, Y.; Xie, T.; Ren, J. Induction of P450 1A by 3-methylcholanthrene protects mice from aristolochic acid-I-induced acute renal injury. Nephrol. Dial. Transplant., 2008, 23(10), 3074-3081.
121. Ross, D. Quinone reductases multitasking in the metabolic world. Drug Metab. Rev., 2004, 36(3-4), 639-654.
122. Ross, D.; Kepa, J.K.; Winski, S.L.; Beall, H.D.; Anwar, A.; Siegel, D. NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms. Chem. Biol. Interact., 2000, 129(1-2), 77-97.
123. Rendic, S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab. Rev., 2002, 34(1-2), 83-448.
124. Rendic, S.; Guengerich, F.P. Update information on drug metabolism systems-2009, part II: summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters. Curr. Drug Metab., 2010, 11(1), 4-84.
125. Rendic, S.; Guengerich, F.P. Contributions of human enzymes in carcinogen metabolism. Chem. Res. Toxicol., 2012, 25(7), 1316-1383.
126. Nebert, D.W.; Jones, J.E. Regulation of the mammalian cyto-chrome P1-450 (CYP1A1) gene. Int. J. Biochem., 1989, 21(3), 243-252.
127. Jaiswal, A. K. Nrf2 signaling in coordinated activation of antioxi-dant gene expression. Free Radic. Biol. Med., 2004, 36(10), 1199-1207.
128. Nioi, P.; Hayes, J.D. Contribution of NAD(P)H:quinone oxi-doreductase 1 to protection against carcinogenesis, and regulation of its gene by the Nrf2 basic-region leucine zipper and the arylhy-drocarbon receptor basic helix-loop-helix transcription factors. Mu-tat. Res., 2004, 555(1-2), 149-171.
129. Li, Y.; Jaiswal, A.K. Human antioxidant-response-element-mediated regulation of type 1 NAD(P)H:quinone oxidoreductase gene expression. Effect of sulfhydryl modifying agents. Eur. J. Biochem., 1994, 226(1), 31-39.
130. Yu, F.Y.; Wu, T.S.; Chen, T.W.; Liu, B.H. Aristolochic acid I induced oxidative DNA damage associated with glutathione depletion and ERK1/2 activation in human cells. Toxicol. In Vitro, 2011 25(4), 810-816.
131. Nebert, D.W.; Roe, A.L.; Dieter, M.Z.; Solis, W.A.; Yang, Y.; Dalton, T.P. Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. Biochem. Pharmacol., 2000, 59(1), 65-85.
132. Burk, O.; Koch, I.; Raucy, J.; Hustert, E.; Eichelbaum, M.; Brock-moller, J.; Zanger, U.M.; Wojnowski, L. The induction of cyto-chrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). J. Biol. Chem., 2004, 279(37), 38379-38385.
133. Toncheva, D.; Dimitrov, T.; Stojanova, S. Etiology of Balkan endemic nephropathy: a multifactorial disease? Eur. J. Epidemiol., 1998, 14(4), 389-394.
134. Stefanovic, V.; Toncheva, D.; Atanasova, S.; Polenakovic, M. Etiology of Balkan endemic nephropathy and associated urothelial cancer. Am. J. Nephrol., 2006, 26(1), 1-11.