Polymorphic ochratoxin A hydroxylation in rat strains phenotyped as poor and extensive metabolizers of debrisoquine.
1. Dark agouti (DA) and Lewis rat strains, which show a genetic polymorphism for debrisoquine-4-hydroxylation, were treated either with a single dose of ochratoxin A (OA) or for 8 weeks with 5 doses per week. Levels of OA and its 4-hydroxy metabolite (4-hydroxy-OA) excreted in urine were determined. 2. At all doses, the metabolic ratio of OA:4-hydroxy-OA was two to five times greater in DA than in Lewis rats, as was the metabolic ratio of debrisoquine:4-hydroxy-debrisoquine. These results are consistent with our previous findings in vitro that hepatic and renal OA 4-hydroxylase activity is three to four times lower in DA than in Lewis rats. These data give further support to the possible co-segregation of genes regulating OA and debrisoquine 4-hydroxylation.
Castegnaro
M
M
International Agency for Research on Cancer, Lyon, France.
Bartsch
H
H
Bereziat
J C
JC
Arvela
P
P
Michelon
J
J
Broussolle
L
L
D000284:Administration, Oral; D000818:Animals; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D005796:Genes; D007546:Isoquinolines / Q000378:metabolism*; D006899:Mixed Function Oxygenases; D009793:Ochratoxins / Q000378:metabolism* / Q000652:urine; D010641:Phenotype; D011110:Polymorphism, Genetic; D051381:Rats; D011917:Rats, Inbred Lew / Q000235:genetics*; D011919:Rats, Inbred Strains / Q000235:genetics*
D007546:Isoquinolines; D009793:Ochratoxins; C025589:ochratoxin A; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; C025650:4-hydroxyochratoxin A; D003647:Debrisoquin