Download Citrinin enhances toxic and genotoxic effects of ochratoxin A, in vitro

CITRININ ENHANCES TOXIC AND GENOTOXIC EFFECTS OF OCHRATOXIN A, IN
VITRO AND IN VIVO
Tozlovanu M. 1, Faucet-Marquis V.1, Molinié A.1, Castegnaro M.2, Manderville R.3 & PfohlLeszkowicz A.1
1
Laboratoire de Génie Chimique, UMR-CNRS/INPT/UPS n° 5503, département Bioprocédés
& Systèmes Microbiens, INP/ENSAT 1 agrobiopôle, 31326 Auzeville-Tolosane, France ; 2
Consultant, Les Collanges, Saint-Jean Chambre, France ; 3 Department of Chemistry and
Biochemistry, University of Guelph, Guelph Ontario, Canada.
e-mail : [email protected]
During storage of cereals, some fungi grow and elaborate Ochratoxin A (OTA) or citrinin
(CIT), nephrotoxic mycotoxins, both suspected to be involved in Balkan endemic
nephropathy and associated urothelial tumours. Both are frequently found in food, notably in
Balkan region. Simultaneous administration of OTA and CIT enhanced the incidence of renal
tumours in male mice. The aim of this study was to determine the cytotoxic and genotoxic
combined effect of CIT and OTA, (i) in cells culture and (ii) in vivo on Dark Agouty rat fed
for 3 weeks with ground wheat enriched with OTA and/or CIT. When the mycotoxins are
simultaneously present, the cytotoxicity is considerably enhanced. Expression of
biotransformation enzymes (CYP, COX, LIPOX) is differently modulated. DNA adducts
patterns of rat kidney after a 3-weeks feeding, are similar to those obtained on cell cultures.
The main OTA DNA-adduct, identified as C8 dG-OTA and found in human tumours, is
increased by simultaneous presence of CIT and OTA.