Effect of strain and diet upon constitutive and chemically induced activities of several xenobiotic-metabolizing enzymes in rats.
The response of animals in toxicity studies reflects a complex interaction of a number of variables, some intrinsic to a particular study design and others resulting from the treatment itself. The influences of strain and diet upon constitutive and benzo(a)pyrene (B(a)P) induced activities of several hepatic Phase I and II enzymes were studied in a multifactoral design. Male and female CDF and Crl:CD rats were fed a standard rodent diet ad libitum, a 75% of ad libitum restricted feeding regimen or a phytoestrogen-free diet for approximately 3 weeks. During the last five days of the study, rats were administered either corn oil (vehicle) or 15 mg/kg/day B(a)P via oral gavage. The constitutive activities of hepatic CYP1A1, CYP1A2, CYP2B1/2, and mixed isoforms of UDP-glucuronosyl transferase, sulfotransferase, and glutathione-S-transferase varied significantly by feeding regimen and strain. Responses to B(a)P administration were also observed to be influenced by diet and strain in a manner similar to that observed for constitutive activities. These findings point out the potentially significant interactions of relatively commonly encountered variables that may affect results of hazard testing, especially when employing near metabolically saturating dosages of test chemicals.
Stott
W T
WT
Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, MI 48674, USA. wtscott@dow.com
Kan
H L
HL
McFadden
L G
LG
Sparrow
B R
BR
Gollapudi
B B
BB
D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019362:Cytochrome P-450 CYP2B1 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004032:Diet; D004790:Enzyme Induction; D005260:Female; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D005982:Glutathione Transferase / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010088:Oxidoreductases / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D015238:Sulfotransferases / Q000096:biosynthesis*; D018675:Toxicity Tests; D015262:Xenobiotics
D015262:Xenobiotics; D001564:Benzo(a)pyrene; D003314:Corn Oil; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases