Effects of 5-bromo-2'deoxyuridine (BrdU) implants on hepatic cytochrome P-450 content and beta-oxidation activity in rats and mice.
Standard regulatory toxicity tests are frequently supplemented with additional compound specific analysis. Analysis of hepatic cytochrome P-450 content, hepatic beta-oxidation activity (biochemical analysis), and cell proliferation rates are examples of these analyses that are included when past experience or similarity to other compounds, suggest that a presently tested compound may have an effect. Until now, separate subsets of animals have been designated for cell proliferation analysis and biochemical analysis, because it was unknown if implantation of 5-bromo-2'deoxyuridine (BrdU) filled osmotic pumps (BrdU implants) would effect the rate of hepatic-beta or hepatic cytochrome P-450 content. The purpose of the current study was to determine if BrdU implants had an effect on hepatic cytochrome P-450 content, beta-oxidation activity, or the measurement of these enzymes in rats and mice. The BrdU was administered through subcutaneous osmotic pump implants. The rate of hepatic peroxisomal beta-oxidation was not altered in male or female rats or mice with the BrdU implants when compared to those of the control groups. The total hepatic cytochrome P-450 content was also not altered in male or female rats or mice with the BrdU implants when compared to those of the control groups. BrdU implants do not appear to have an effect on the rate of hepatic peroxisomal beta-oxidation or the total hepatic cytochrome P-450 content in male or female rats and mice. It can be concluded that in future studies, rats or mice which are designated for cell proliferation analysis using BrdU implants are also suitable for use in evaluating chemically induced effects on hepatic peroxisomal beta-oxidation activity and/or total hepatic cytochrome P-450 content.
Biegel
L B
LB
E. I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE 19714, USA.
Applegate
M
M
Sulecki
L M
LM
D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004343:Drug Implants; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D004343:Drug Implants; D003577:Cytochrome P-450 Enzyme System; D001973:Bromodeoxyuridine