Species and strain sensitivity to the induction of peroxisome proliferation by chloroacetic acids.
B6C3F1 mice and Sprague-Dawley rats were provided drinking water containing 6-31 mM (1-5 g/liter) trichloroacetic acid (TCA), 8-39 mM (1-5 g/liter) dichloroacetic acid (DCA), or 11-32 mM (1-3 g/liter) monochloroacetic acid (MCA) for 14 days. TCA and DCA, but not MCA, increased the mouse relative liver weight in a dose-dependent manner. Rat liver weights were not altered by TCA or DCA treatment, but were depressed by MCA. Hepatic peroxisome proliferation was demonstrated by (1) increased palmitoyl-CoA oxidase and carnitine acetyl transferase activities, (2) appearance of a peroxisome proliferation-associated protein, and (3) morphometric analysis of electron micrographs. Mouse peroxisome proliferation was enhanced in a dose-dependent manner by both TCA and DCA, but only the high DCA concentration (39 mM) increased rat liver peroxisome proliferation. MCA was ineffective in both species. Three other mouse strains (Swiss-Webster, C3H, and C57BL/6) and two strains of rat (F344 and Osborne-Mendel) were examined for sensitivity to TCA. TCA (12 and 31 mM) effectively enhanced peroxisome proliferation in all mouse strains, especially the C57BL/6. A more modest enhancement in the Osborne-Mendel (288%) and F344 rat (167%) was seen. Dosing F344 rats with 200 mg/kg TCA in water or corn oil for 10 days increased peroxisome proliferation 179 and 278%, respectively, above the vehicle controls. These studies demonstrate that the mouse is more sensitive than the rat with respect to the enhancement of liver peroxisome proliferation by TCA and DCA and suggest that if peroxisome proliferation is critical for the induction of hepatic cancer by TCA and DCA, then the rat should be less sensitive or refractory to tumor induction.
DeAngelo
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AB
Genetic Toxicology Division, U.S. Environmental Protection Agency, Cincinnati, Ohio 45268.
Daniel
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FB
McMillan
L
L
Wernsing
P
P
Savage
R E
RE
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D002332:Carnitine O-Acetyltransferase / Q000378:metabolism; D003314:Corn Oil / Q000032:analysis; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D008099:Liver / Q000032:analysis / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008830:Microbodies / Q000032:analysis / Q000187:drug effects / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D014677:Pharmaceutical Vehicles; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014238:Trichloroacetic Acid / Q000494:pharmacology*; D014867:Water / Q000032:analysis
D000085:Acetates; D002273:Carcinogens; D014677:Pharmaceutical Vehicles; D014867:Water; C006972:chloroacetic acid; D014238:Trichloroacetic Acid; D003314:Corn Oil; D003999:Dichloroacetic Acid; D002332:Carnitine O-Acetyltransferase