Structures of covalent adducts between DNA and ochratoxin a: a new factor in debate about genotoxicity and human risk assessment

Chemical Research in Toxicology
Peter G MantleA Pfohl-Leszkowicz

Abstract

The potent renal carcinogenicity of ochratoxin A (OTA) in rats, principally in the male, raises questions about mechanism. Chromatographic evidence of DNA adducts after (32)P-postlabeling analysis contrasts with experimental attempts to demonstrate the absence of OTA in such adducts. Proffered schemes for alternative epigenetic mechanisms in OTA carcinogenicity remain unsatisfying, while structural data substantiating DNA-OTA adducts has also been lacking. We report refined (32)P-postlabeling methodology revealing one principal adduct isolated in small amounts from the kidneys of all five Fischer and five Dark Agouti rats to which OTA had been given on four consecutive days. We also describe structural data for the principal adduct from OTA/DNA interaction in vitro and its subsequent preparative isolation by the postlabeling methodology (as C-C8 OTA 3'dGMP), essentially creating an ochratoxin B-guanine adduct. Reasoning for the unsuitability of experimental protocols in published evidence claiming nongenotoxicity of OTA is given. In vivo exposure of renal DNA to cycles of adduction with OTA, necessarily protracted for carcinogenesis to occur, can reasonably explain an occasional focal neoplasm from which metastasizing carcinoma...Continue Reading

References

Dec 23, 1991·Proceedings. Biological Sciences·P G MantleD R Turner
Feb 7, 1998·Hypertension·A Garcia-SanzJ C Romero
Jun 25, 1998·International Journal of Cancer. Journal International Du Cancer·M CastegnaroH Bartsch
Feb 15, 2001·Chemical Research in Toxicology·J GautierR J Turesky
Mar 27, 2003·Journal of the American Chemical Society·Jian DaiRichard A Manderville
Apr 25, 2003·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Ana MiljkovicPeter G Mantle
Oct 14, 2003·Toxicology and Applied Pharmacology·Herbert ZepnikWolfgang Dekant
Feb 18, 2004·Chemical Research in Toxicology·Angela MallyWolfgang Dekant
Sep 21, 2004·Chemical Research in Toxicology·Virginie FaucetRichard A Manderville
Jul 19, 2005·Chemical Research in Toxicology·Robert J Turesky
Jul 19, 2005·Chemical Research in Toxicology·Richard A Manderville
Aug 16, 2005·Chemical Research in Toxicology·Angela MallyPasquale Mosesso
Nov 26, 2005·Archives of Toxicology·William J WaddellGary M Williams
Dec 8, 2005·Food Additives and Contaminants·Peter MantleSandra Nestler
Dec 8, 2005·Food Additives and Contaminants·A Pfohl-Leszkowicz, M Castegnaro
May 23, 2006·Molecular Nutrition & Food Research·Marcel CastegnaroAnnie Pfohl-Leszkowicz
Aug 11, 2006·Human & Experimental Toxicology·W J Waddell
Sep 19, 2006·Chemical Research in Toxicology·Mariana TozlovanuRichard A Manderville
Dec 30, 2006·Molecular Nutrition & Food Research·Annie Pfohl-Leszkowicz, Richard A Manderville
Mar 9, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Eva RachedAngela Mally
Jul 17, 2007·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Amy L BrownPeter G Mantle
Feb 26, 2008·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Peter G Mantle
Apr 3, 2008·Molecular Nutrition & Food Research·Thierry DelatourChristophe Cavin
Jan 6, 2009·Molecular Nutrition & Food Research·Annie Pfohl-LeszkowiczRichard A Manderville
May 19, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A VettorazziA López de Cerain
May 27, 2009·Mutation Research·George E JohnsonGareth J Jenkins
Jul 7, 2009·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Peter G Mantle

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Citations

Feb 15, 2012·Analytical and Bioanalytical Chemistry·Vasilica LatesJean-Louis Marty
Aug 10, 2010·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·Peter Mantle, Elena Kulinskaya
Dec 15, 2010·DNA and Cell Biology·Hao-Yu ShenJia Li
May 10, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Kristin CzakaiAngela Mally
May 31, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Daisuke HibiTakashi Umemura
Jul 22, 2011·Journal of Toxicology·M Marin-KuanB Schilter
Jan 12, 2010·Arhiv za higijenu rada i toksikologiju·Annie Pfohl-Leszkowicz
Sep 28, 2013·International Journal of Molecular Sciences·Robert RadfordTara McMorrow
Apr 1, 2010·Toxins·Lalini Reddy, Kanti Bhoola
Jun 1, 2010·Toxins·Stjepan Pepeljnjak, Maja Šegvić Klarić
Jul 22, 2010·Toxins·Jamie E Jennings-GeeGary G Schwartz
Oct 25, 2013·Toxins·Valeria SorrentiFabio Galvano
Nov 6, 2013·Toxins·Maja Segvić KlarićMaja Peraica
Nov 28, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ajit KumarLuciano Saso
Nov 11, 2011·Kidney International·Bojan JelakovićKathleen G Dickman
Sep 18, 2015·Journal of Biochemical and Molecular Toxicology·Yu ZhangWentao Xu
Mar 18, 2016·Environmental Toxicology and Pharmacology·L N CariddiA M Dalcero
Mar 31, 2016·Toxins·Chit Shing Jackson Woo, Hani El-Nezami
Apr 14, 2015·Environmental Toxicology and Pharmacology·L N CariddiA M Dalcero
Jul 10, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·L A CorcueraA López de Cerain
Dec 3, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Cyndia A González-AriasAurora E Rojas-García
Apr 29, 2014·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A G Marroquín-CardonaA W Hayes
Oct 9, 2014·Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment·A Pfohl-LeszkowiczJ Fink-Gremmels
Aug 20, 2016·Archives of Toxicology·Marie StiborováHeinz H Schmeiser
Nov 2, 2016·Chemical Research in Toxicology·Richard A Manderville, Stacey D Wetmore
Jan 27, 2012·Critical Reviews in Toxicology·Lois A HaightonEarle R Nestmann
Feb 20, 2015·Toxicologic Pathology·Genevieve S BondyRekha Mehta

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