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000119616 0247_ $$2doi$$a10.1016/j.mrgentox.2014.01.012
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000119616 0247_ $$2ISSN$$a1879-3592
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000119616 1001_ $$aBárta, František$$b0
000119616 245__ $$aThe effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats--a comparative study.
000119616 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2014
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000119616 520__ $$aAristolochic acid is the cause of aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN) and their associated urothelial malignancies. Using Western blotting, we investigated the expression ofquinone oxidoreductase (NQO1), the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI) in mice and rats. In addition, the effect of AAI on the expression of the NQO1 protein and its enzymatic activity in these experimental animal models was examined. We found that NQO1 protein levels in cytosolic fractions isolated from liver, kidney and lung of mice differed from those expressed in these organs of rats. In mice, the highest levels of NQO1 protein and NQO1 activity were found in the kidney, followed by lung and liver. In contrast, the NQO1 protein levels and enzyme activity were lowest in rat-kidney cytosol, whereas the highest amounts of NQO1 protein and activity were found in lung cytosols, followed by those of liver. NQO1 protein and enzyme activity were induced in liver and kidney of AAI-pretreated mice compared with those of untreated mice. NQO1 protein and enzyme activity were also induced in rat kidney by AAI. Furthermore, the increase in hepatic and renal NQO1 enzyme activity was associated with AAI bio-activation and elevated AAI-DNA adduct levels were found in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, our results indicate that AAI can increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential.
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000119616 650_7 $$2NLM Chemicals$$aAristolochic Acids
000119616 650_7 $$2NLM Chemicals$$aCarcinogens
000119616 650_7 $$094218WFP5T$$2NLM Chemicals$$aaristolochic acid I
000119616 650_7 $$0EC 1.6.5.2$$2NLM Chemicals$$aNAD(P)H Dehydrogenase (Quinone)
000119616 650_7 $$0EC 1.6.5.2$$2NLM Chemicals$$aNQO1 protein, rat
000119616 650_7 $$0EC 1.6.5.2$$2NLM Chemicals$$aNqo1 protein, mouse
000119616 7001_ $$aLevová, Kateřina$$b1
000119616 7001_ $$0P:(DE-HGF)0$$aFrei, Eva$$b2
000119616 7001_ $$0P:(DE-He78)5e6f79f3c71682d052bc2536749ca077$$aSchmeiser, Heinz$$b3$$udkfz
000119616 7001_ $$aArlt, Volker M$$b4
000119616 7001_ $$aStiborová, Marie$$b5
000119616 773__ $$0PERI:(DE-600)2210272-3$$a10.1016/j.mrgentox.2014.01.012$$gVol. 768, p. 1 - 7$$p1 - 7$$tMutation research / Genetic toxicology and environmental mutagenesis$$v768$$x1383-5718$$y2014
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