Premium
Mycotoxins and the kidney: Modes of action for renal tumor formation by ochratoxin A in rodents
Author(s) -
Mally Angela,
Dekant Wolfgang
Publication year - 2009
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200800149
Subject(s) - ochratoxin a , oxidative stress , carcinogen , population , mycotoxin , dna adduct , dna damage , kidney , mode of action , ochratoxin , biology , chemistry , dna , pharmacology , endocrinology , toxicology , biochemistry , food science , medicine , environmental health
The mycotoxin ochratoxin A (OTA) is a potent renal carcinogen in rodents. OTA is only slowly eliminated due to high affinity to plasma proteins and inefficient biotransformation. A number of mechanisms have been proposed to account for renal tumor formation. DNA adduct formation, mainly based on the 32 P‐postlabeling assay, was postulated as a mode of action (MoA). However, studies using radiolabeled OTA or MS failed to demonstrate formation of OTA‐derived DNA‐adducts. While some studies have demonstrated generation of oxidative stress by OTA, the oxidative stress response appears to be not very pronounced and therefore may not explain the high potency of OTA in rodents. A number of recent investigations support the hypothesis that OTA causes disruption of mitosis resulting in blocked or asymmetric cell division. This may present an increased risk of aneuploidy acquisition and may play a critical role in OTA‐induced tumor formation. The absence of DNA‐adducts derived from OTA supports a thresholded MoA, and a tolerable weekly intake (TWI) of 120 ng OTA/kg bw has been derived by the European Food Safety Authority. The estimated intake of OTA in Europe is below this TWI for most of the population.