Structures of Covalent Adducts between DNA and Ochratoxin A: A New Factor in Debate about Genotoxicity and Human Risk Assessment - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Chemical Research in Toxicology Année : 2010

Structures of Covalent Adducts between DNA and Ochratoxin A: A New Factor in Debate about Genotoxicity and Human Risk Assessment

Résumé

The potent renal carcinogenicity of ochratoxin A (OTA) in rats, principally in the male, raises questions about mechanism. Chromatographic evidence of DNA adducts after 32P-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 32P-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 could develop.
Fichier principal
Vignette du fichier
Mantle_5719.pdf (499.25 Ko) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03474392 , version 1 (10-12-2021)

Identifiants

Citer

Peter G. Mantle, Virginie Faucet-Marquis, Richard A. Manderville, Bianca Squillaci, Annie Pfohl-Leszkowicz. Structures of Covalent Adducts between DNA and Ochratoxin A: A New Factor in Debate about Genotoxicity and Human Risk Assessment. Chemical Research in Toxicology, 2010, 23 (1), pp.89-98. ⟨10.1021/TX900295a⟩. ⟨hal-03474392⟩
8 Consultations
51 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More