Effects of joint exposures to selected peroxisome proliferators on hepatic acyl-CoA oxidase activity in male B6C3F1 mice.
The interaction potential of peroxisome proliferators of similar and dissimilar structure was examined in B6C3F1 mice. Mice were fed diets containing varying concentrations of ciprofibrate (Cipro), clofibrate (Clof) or di(2-ethylhexyl)phthalate (DEHP), or combinations of Cipro and Clof or Cipro and DEHP for 4 d. Induction of peroxisomal beta-oxidation, measured by increased acyl-CoA oxidase activity, was used as the endpoint for analysis. An additive response occurred following joint exposure to the structurally related compounds Cipro and Clof, whereas a possible synergistic response occurred at low dose combinations of the structurally dissimilar Cipro and DEHP. These findings represent the first report assessing the in-vivo interaction potential of structurally similar and dissimilar peroxisome proliferators and provides insight into the dose-response nature of joint exposures to certain non-genotoxic carcinogens.
Environmental Health Sciences Program, School of Public Health, University of Massachusetts, Amherst 01003.
J B
JB
Ochs
L A
LA
Baldwin
D A
DA
Leonard
E J
EJ
Calabrese
D042962:Acyl-CoA Oxidase; D000818:Animals; D002994:Clofibrate / Q000008:administration & dosage* / Q000494:pharmacology; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004051:Diethylhexyl Phthalate / Q000008:administration & dosage* / Q000494:pharmacology; D058607:Fibric Acids; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008830:Microbodies / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism*
D058607:Fibric Acids; D000960:Hypolipidemic Agents; D002995:Clofibric Acid; D004051:Diethylhexyl Phthalate; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; C019304:ciprofibrate; D002994:Clofibrate