DNA adduct formation by ochratoxin A: Review of the available evidence

The mycotoxin ochratoxin A (OTA) is a potent nephrotoxin and renal carcinogen in rodents. However, the mechanism of OTA-induced tumour formation is unknown and conflicting results regarding the potential of OTA to react with DNA have been obtained. While experiments using radiolabelled (H-3 or C-14) OTA and liquid scintillation counting or accelerator mass spectrometry indicate lack of formation of covalent DNA-adducts, spots detected by (32)p-postlabelling have been attributed to treatment with OTA. However, these putative DNA-adducts have not been shown to contain OTA or part of the OTA molecule and so far no structural information has been provided. Consistent with the absence of DNA-binding of radiolabelled OTA, studies on biotransformation in vivo and in vitro indicate that OTA is poorly metabolized and does not form reactive intermediates capable of interacting with DNA. Recently however, the structures of a carbon- and an oxygen-bonded OTA-deoxyguanosine adduct which is formed by photoirradiation of OTA in the presence of deoxyguanosine have been reported and suggested to be involved in OTA carcinogenicity. The aim of this manuscript is to provide an overview of the available literature regarding DNA adduct formation by OTA.