scholarly journals 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

2004 ◽  
Vol 113 (2) ◽  
pp. 189-197 ◽  
Author(s):  
Marie Stiborová ◽  
Eva Frei ◽  
Petr Hodek ◽  
Manfred Wiessler ◽  
Heinz H. Schmeiser
Keyword(s):  
Dna Adducts ◽  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Cytochromes P450 ◽  
Prostaglandin H Synthase ◽  
P450 Reductase ◽  
Prostaglandin H ◽  
Nadph:Cytochrome P450 Reductase

Role of hepatic cytochromes P450 in bioactivation of the anticancer drug ellipticine: Studies with the hepatic NADPH:Cytochrome P450 reductase null mouse

2008 ◽  
Vol 226 (3) ◽  
pp. 318-327 ◽  
Author(s):  
Marie Stiborová ◽  
Volker M. Arlt ◽  
Colin J. Henderson ◽  
C. Roland Wolf ◽  
Věra Kotrbová ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Cytochromes P450 ◽  
Null Mouse ◽  
P450 Reductase ◽  
Nadph:Cytochrome P450 Reductase

DNA adducts formed by ring-oxidation of the carcinogen 2-naphthylamine with prostaglandin H synthase in vitro and in the dog urothelium in vivo

1985 ◽  
Vol 6 (9) ◽  
pp. 1379-1387 ◽  
Author(s):  
Y. Yamazoe ◽  
D.W. Miller ◽  
C.C. Weis ◽  
K.L. Dooley ◽  
T.V. Zenser ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Prostaglandin H Synthase ◽  
Ring Oxidation ◽  
Prostaglandin H

scholarly journals Induction of cytochromes P450 1A1 and 1A2 suppresses formation of DNA adducts by carcinogenic aristolochic acid I in rats in vivo

Toxicology ◽  
2016 ◽  
Vol 344-346 ◽  
pp. 7-18 ◽  
Author(s):  
Helena Dračínská ◽  
František Bárta ◽  
Kateřina Levová ◽  
Alena Hudecová ◽  
Michaela Moserová ◽  
...  
Keyword(s):  
Dna Adducts ◽  
Aristolochic Acid ◽  
Cytochromes P450 ◽  
Aristolochic Acid I

To the Mechanism of 2-Nitroanisole Carcinogenicity: in vitro Metabolism of 2-Nitroanisole Mediated by Peroxidasesand Xanthine Oxidase

1998 ◽  
Vol 63 (6) ◽  
pp. 857-869 ◽  
Author(s):  
Marie Stiborová ◽  
Heinz H. Schmeiser ◽  
Eva Frei
Keyword(s):  
Horseradish Peroxidase ◽  
Xanthine Oxidase ◽  
Dna Adducts ◽  
Active Oxygen Species ◽  
Radical Mechanism ◽  
Maximal Velocity ◽  
Prostaglandin H Synthase ◽  
Nuclease P1 ◽  
Prostaglandin H

The in vitro enzymatic metabolism of carcinogenic 2-nitroanisole was investigated using peroxidases (horseradish peroxidase and prostaglandin H synthase) and xanthine oxidase catalyzing oxidative and reductive reactions, respectively. The oxidation of 2-nitroanisole catalyzed by horseradish peroxidase exhibits the Michaelis-Menten kinetics. The Michaelis constant (Km) and the maximal velocity (Vmax) values for this substrate were determined at pH 5.0, 7.0, 7.6 and 8.0. At optimal pH (7.6), the Km and Vmax values are 0.219 μmol/l and 34.45 pmol/min per nmol peroxidase, respectively. The oxidation of 2-nitroanisole is inhibited by radical trapping agents (NADH, ascorbate, glutathione and nitrosobenzene). This indicates that the peroxidase-mediated oxidation of 2-nitroanisole proceeds via a radical mechanism. Active oxygen species are formed during the horseradish peroxidase-catalyzed reactions in the presence of NADH, hydrogen peroxide and 2-nitroanisole. 2-Nitroanisole is also oxidized by mammalian prostaglandin H synthase. Using the nuclease P1-enhanced variation of the 32P-postlabelling assay, the formation of DNA adducts was detected in DNA treated with 2-nitroanisole and xanthine oxidase. No DNA binding was detected after oxidation of 2-nitroanisole with horseradish peroxidase and prostaglandin H synthase. The results presented (the formation of DNA adducts after 2-nitroanisole activation by xanthine oxidase and that of radicals and/or superoxide radicals during the reactions with peroxidases) strongly suggest the participation of 2-nitroanisole both in the initiation and in the promotion phases of carcinogenesis.

scholarly journals Contribution of biotransformation enzymes to the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions, difficult answers

2008 ◽  
Vol 1 (1) ◽  
pp. 8-12 ◽  
Author(s):  
Marie Stiborová ◽  
Jiří Hudeček ◽  
Eva Frei ◽  
Heinz Schmeiser
Keyword(s):  
Renal Injury ◽  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Cytochromes P450 ◽  
Balkan Endemic Nephropathy ◽  
Kidney Fibrosis ◽  
Relative Contribution ◽  
Biotransformation Enzymes ◽  
Endemic Nephropathy

Contribution of biotransformation enzymes to the development of renal injury and urothelial cancer caused by aristolochic acid: urgent questions, difficult answersIngestion of aristolochic acid (AA) is associated with the development of aristolochic acid nephropathy, which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA may also cause a similar type of kidney fibrosis with malignant transformation of the urothelium, the Balkan endemic nephropathy. Understanding which enzymes are involved in AA activation and/or detoxication is important in the assessment of a susceptibility to this carcinogen. The most important human enzymes activating AA by simple nitroreductionin vitroare hepatic and renal cytosolic NAD(P)H:quinone oxidoreductase, hepatic microsomal cytochrome P450 1A2 and renal microsomal NADPH:cytcohrome P450 reductase, besides cyclooxygenase, which is highly expressed in urothelial tissue. Despite extensive research, contribution of most of these enzymes to the development of these diseases is still unknown. Hepatic cytochromes P450 were found to detoxicate AA in mice, and thereby protect the kidney from injury. However, which of cytochromes P450 are the most important in this process both in animal models and in humans have not been entirely resolved as yet. In addition, the relative contribution of enzymes found to activate AA to species responsible for induction of urothelial cancer in humans remains still to be resolved.

Enzymes Metabolizing Aristolochic Acid and their Contribution to the Development of Aristolochic Acid Nephropathy and Urothelial Cancer

2013 ◽  
Vol 14 (6) ◽  
pp. 695-705 ◽  
Author(s):  
Marie Stiborova ◽  
Vaclav Martínek ◽  
Eva Frei ◽  
Volker Arlt ◽  
Heinz Schmeiser
Keyword(s):  
Urothelial Cancer ◽  
Aristolochic Acid ◽  
Aristolochic Acid Nephropathy

scholarly journals Heme coordination of prostaglandin H synthase.

1993 ◽  
Vol 268 (12) ◽  
pp. 8554-8563
Author(s):  
A.L. Tsai ◽  
R.J. Kulmacz ◽  
J.S. Wang ◽  
Y. Wang ◽  
H.E. Van Wart ◽  
...  
Keyword(s):  
Prostaglandin H Synthase ◽  
Prostaglandin H
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