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SPECIES AND STRAIN SENSITIVITY TO THE INDUCTION OF PEROXISOME PROLIFERATION BY CHLOROACETIC ACIDS
Citation:
DeAngelo, A.B., F. Daniel, L. McMillan, P. Wernsing, AND R. Savage, Jr. SPECIES AND STRAIN SENSITIVITY TO THE INDUCTION OF PEROXISOME PROLIFERATION BY CHLOROACETIC ACIDS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-89/245 (NTIS PB90135393).
Description:
B6C3F1 mice and Sprague-Dawley rats were provided drinking water containing 6 - 31 mM trichloroacetic acid (TCA), 8 - 39 mM dichloroacetic acid (DCA) or 11 - 33 mM monochloroacetic acid (MCA) for 14 days. CA and DCA, but not MCA, increased the mouse relative liver weight in a dose dependent manner. at liver weights were not altered by TCA and DCA treatment, but were depressed by MCA. epatic peroxisome proliferation was demonstrated by (1) increased palmitoyl CoA oxidase activity (PCO), (2) appearance of a peroxisome proliferation-associated (PP-A) protein, and (3) morphometric analysis by electron microscopy. ouse peroxiaome 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. CA was inactive in both species. hree other mouse strains (Swiss-Webster, C3H, and C57BL/6) and two strains of rat (F344 and Osborne-Mendel) were examined for sensitivity to TCA. CA (12 and 31 mM) effectively enhanced peroxisome proliferation in all mice strains, especially the C57BL/6. ore modest enhancement in the Osborne-Mendel (288%) and F344 rat (167%) was seen. osing 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. orn oil potentiated the TCA effect (316% above the water vehicle). hese 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 sufficient for the induction of hepatic cancer by TCA and DCA, then the rat should be less sensitive or refractory to tumor induction.