The effects of perfluoro-octanoic acid on hepatic peroxisome proliferation and related parameters show no sex-related differences in mice.
Male and female C57Bl/6 mice were administered perfluor-octanoic acid PFOA; 0.02-0.05% w/w; 5-10 days) in their diet. This treatment resulted in a several-fold induction of hepatic peroxisomal fatty acid beta-oxidation (monitored as increases in cyanide-insensitive palmitoyl-CoA oxidation, lauroyl-CoA oxidase and catalase activity) in all animals. The protein content of the hepatic mitochondrial fraction was also increased in all mice exposed to PFOA. Furthermore, studies on xenobiotic-metabolizing enzymes revealed no sex-related difference in the response to PFOA. All mice demonstrated a dramatic increase in omega-hydroxylation of lauric acid. Cytosolic epoxide hydrolase, glutathione transferase and DT-diaphorase activities were increased about 2-5-fold. These results with mice differ dramatically from previous studies and our own experiments here with Wistar rats, in which exposure to PFOA causes hepatic peroxisome proliferation in male animals, whereas females are unaffected.
Sohlenius
A K
AK
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Andersson
K
K
DePierre
J W
JW
D000818:Animals; D002210:Caprylates / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008830:Microbodies / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics
D002210:Caprylates; D005466:Fluorocarbons; D007850:Lauric Acids; D011506:Proteins; C030358:lauric acid; D010171:Palmitoyl Coenzyme A; C023036:perfluorooctanoic acid; D002374:Catalase