PMID- 19414514
OWN - NLM
STAT- MEDLINE
DCOM- 20090908
LR  - 20161125
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 110
IP  - 1
DP  - 2009 Jul
TI  - Ochratoxin A-mediated DNA and protein damage: roles of nitrosative and oxidative 
      stresses.
PG  - 84-94
LID - 10.1093/toxsci/kfp090 [doi]
AB  - Ochratoxin A (OTA) is a mycotoxin occurring in a variety of foods. OTA is 
      nephrotoxic and nephrocarcinogenic in rodents. An OTA-mediated increase of the 
      inducible nitric oxide synthase (iNOS) expression was observed in normal rat 
      kidney renal cell line and in rat hepatocyte cultures, suggesting the induction 
      of nitrosative stress. This was associated with an increased nuclear factor 
      kappa-light chain enhancer of activated B cells activity. The potential 
      consequences of iNOS induction were further investigated. A significant increase 
      in the levels of protein nitrotyrosine residues was observed with OTA. In 
      addition, OTA was found to increase the level of DNA abasic sites in both cell 
      cultures system. This end point was used as an indirect measure of 8-nitroguanine 
      formation. Treatment of the cells with L-N(6)-(1-iminoethyl) lysine, a specific 
      inhibitor of iNOS activity, inhibited the OTA-mediated overnitration of proteins 
      but did not reduce the level of DNA abasic sites. It was found previously that 
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) activators were able to 
      restore the cellular defense against oxidative stress and could prevent DNA 
      abasic sites in cell cultures. In the present study, pretreatment of the cells 
      with activators of Nrf2 prevented OTA-mediated increase in lipid peroxidation, 
      confirming the potential of Nrf2 activators to confer protection against 
      OTA-mediated oxidative stress. In addition, it was found that Nrf2 activators 
      could also prevent OTA-induced protein nitration and cytotoxicity. In conclusion, 
      the present data further confirm oxidative stress as a key source of OTA-induced 
      DNA damage and provide additional evidence for a role of this mechanism in OTA 
      carcinogenicity. The exact role of nitrosative stress still remains to be 
      established.
FAU - Cavin, Christophe
AU  - Cavin C
AD  - Quality and Safety Department, Nestle Research Center, Vers-chez-les-Blanc, 
      CH-1000 Lausanne 26, Switzerland. christophe.cavin@rdls.nestle.com
FAU - Delatour, Thierry
AU  - Delatour T
FAU - Marin-Kuan, Maricel
AU  - Marin-Kuan M
FAU - Fenaille, Francois
AU  - Fenaille F
FAU - Holzhauser, Daisy
AU  - Holzhauser D
FAU - Guignard, Gabriela
AU  - Guignard G
FAU - Bezencon, Claudine
AU  - Bezencon C
FAU - Piguet, Dominique
AU  - Piguet D
FAU - Parisod, Veronique
AU  - Parisod V
FAU - Richoz-Payot, Janique
AU  - Richoz-Payot J
FAU - Schilter, Benoit
AU  - Schilter B
LA  - eng
PT  - Journal Article
DEP - 20090504
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Aldehydes)
RN  - 0 (Carcinogens)
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (NF-E2 Transcription Factor, p45 Subunit)
RN  - 0 (NF-kappa B)
RN  - 0 (Ochratoxins)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
RN  - 1779SX6LUY (ochratoxin A)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - K1CVM13F96 (4-hydroxy-2-nonenal)
SB  - IM
MH  - Aldehydes/pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Carcinogens/*toxicity
MH  - Chromatography, High Pressure Liquid
MH  - Cysteine Proteinase Inhibitors/pharmacology
MH  - *DNA Damage/drug effects
MH  - Electrophoretic Mobility Shift Assay
MH  - Heme Oxygenase-1/biosynthesis
MH  - Male
MH  - NF-E2 Transcription Factor, p45 Subunit/genetics
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - Ochratoxins/*toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Nitrogen Species/*toxicity
MH  - Reactive Oxygen Species/*toxicity
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - Tandem Mass Spectrometry
EDAT- 2009/05/06 09:00
MHDA- 2009/09/09 06:00
CRDT- 2009/05/06 09:00
PHST- 2009/05/06 09:00 [entrez]
PHST- 2009/05/06 09:00 [pubmed]
PHST- 2009/09/09 06:00 [medline]
AID - kfp090 [pii]
AID - 10.1093/toxsci/kfp090 [doi]
PST - ppublish
SO  - Toxicol Sci. 2009 Jul;110(1):84-94. doi: 10.1093/toxsci/kfp090. Epub 2009 May 4.