Alterations in the integrity of peroxisomal membranes in livers of mice treated with peroxisome proliferators.

Catalase leakage from its particulate compartment within the light mitochondrial fraction of liver was used as an index of the integrity of peroxisomes in untreated mice and in mice treated with the peroxisome proliferators clofibrate(ethyl-p-chlorophenoxyisobutyrate), Wy-14,643(4-chloro-6[2,3-xylidino)-2-pyrimidinylthio]acetic acid) and DEHP(di-(2-ethylhexyl)phthalate). Catalase leakage represented about 2% of the total catalase activity when fractions from untreated mice were incubated at 4 degrees C, increasing to about 5% during 60 min incubation at 37 degrees C. In fractions from livers of mice treated with peroxisome proliferators, catalase leakage was significantly higher, being 7-11% at 4 degrees C and increasing to approximately 20% after 60 min incubation at 37 degrees C. The pattern of release was similar for all proliferators. Parallel data were obtained for catalase latency in these fractions, i.e. following 60 min incubation at 37 degrees C, free (non-latent) catalase activity was 18% in control mice and 65, 67, and 83% in fractions from clofibrate-, Wy-14,643- and DEHP-treated mice, respectively. Differences in catalase leakage from peroxisomes in fractions from untreated mice and clofibrate-treated mice were also apparent following treatments designed to effect membrane permeabilization, as in freeze-thawing, osmotic rupture, and extraction with Triton X-100 and lysophosphatidylcholine. These data are consistent with a significant alteration in the integrity of the membranes of peroxisomes in livers of mice which have been treated with peroxisome proliferators, and furthermore indicate a commonality of effect of these agents.