Binding of ochratoxin A to a urinary globulin: a new concept to account for gender difference in rat nephrocarcinogenic responses

Int J Mol Sci. 2008 May;9(5):719-735. doi: 10.3390/ijms9050719. Epub 2008 May 8.

Abstract

SDS-gradient mini-gel electrophoresis and immunoblotting of urine of rats given ochratoxin A (OTA), showed OTA binding to an alpha2u-globulin. Perceived potential internalised delivery of OTA to proximal tubule epithelia by the carrier, specific only to adult male rats and augmenting other uptake mechanisms, suggests that some experimental nephrotoxicological data may not be appropriate for human risk assessment. Reexamination of female rat renal tumour histopathology of the NTP high dose OTA study showed all carcinomas were solitary, unilateral, microscopic and clinically insignificant at the 2-year end-stage. The novel concept, when consolidated further from our archived material, may moderate current perceptions of the human risk of traces of dietary OTA.

Keywords: Ochratoxin A; evidence-based toxicology; female rat; gel electrophoresis; immunoblotting; mycotoxin; nephrotoxicity; renal carcinoma; risk assessment; α2u-globulin.