TY  - JOUR
AU  - Bárta, František
AU  - Levová, Kateřina
AU  - Frei, Eva
AU  - Schmeiser, Heinz
AU  - Arlt, Volker M
AU  - Stiborová, Marie
TI  - The effect of aristolochic acid I on expression of NAD(P)H:quinone oxidoreductase in mice and rats-a comparative study.
JO  - Mutation research / Genetic toxicology and environmental mutagenesis
VL  - 768
SN  - 1383-5718
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DKFZ-2017-00247
SP  - 1 - 7
PY  - 2014
AB  - Aristolochic 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.
KW  - Aristolochic Acids (NLM Chemicals)
KW  - Carcinogens (NLM Chemicals)
KW  - aristolochic acid I (NLM Chemicals)
KW  - NAD(P)H Dehydrogenase (Quinone) (NLM Chemicals)
KW  - NQO1 protein, rat (NLM Chemicals)
KW  - Nqo1 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:24769487
DO  - DOI:10.1016/j.mrgentox.2014.01.012
UR  - https://inrepo02.dkfz.de/record/119616
ER  -