Sex- and strain-specific induction of renal tumors by ochratoxin A in rats correlates with DNA adduction.
Int J Cancer
; 77(1): 70-5, 1998 Jul 03.
Article
en En
| MEDLINE
| ID: mdl-9639396
Ochratoxin A (OTA), a nephrotoxic and carcinogenic mycotoxin, has been implicated as an etiologic agent in the Balkan endemic nephropathy (BEN), a chronic disease affecting populations in the Balkans. Compared with unaffected individuals, patients suffering from BEN and/or urinary tract tumors were more frequently found to have a capacity for rapid debrisoquine (DB) metabolism, a metabolic reaction related mostly to cytochrome P450 (CYP) 2D in humans. Earlier studies, using female DA and Lewis rats phenotyped as poor or extensive DB metabolizers respectively, revealed a parallelism between DB-4 hydroxylation and OTA-4 hydroxylation. To investigate whether genetic polymorphism modifies tumor induction, we have compared both OTA-induced renal carcinogenicity and DNA adducts in DA and Lewis rats of both sexes. OTA induced renal adenocarcinoma, DA male rats being most responsive, while DA females were resistant. Lewis rats showed an intermediate renal tumor response. OTA also induced malignant transitional cell carcinomas of the bladder in DA male rats only. DNA adducts in the kidney, as judged by the nature of spots and prevalence in OTA-treated animals, were significantly correlated with renal carcinogenicity of OTA, being highest in DA males and lowest in DA females. A parallelism between karyomegalies and tumors of the kidney was observed. In conclusion, our results classify OTA as a genotoxic carcinogen in rats, with sex-specific response controlled in part by drug-metabolizing enzymes that convert OTA into reactive intermediates.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinógenos
/
Aductos de ADN
/
Neoplasias Renales
/
Neoplasias Experimentales
/
Ocratoxinas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Cancer
Año:
1998
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Estados Unidos