Induction of peroxisome proliferation in hepatocytes transplanted into the anterior chamber of the eye. A model system for the evaluation of xenobiotic-induced effects

Abstract

The effect of two hypolipidemic peroxisome proliferators, ciprofibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatocytes transplanted into the anterior chamber of the eye was examined. Young male F-344 rats transplanted with dissociated hepatocytes were fed either a control diet or a diet containing 0.025% ciprofibrate or 2% DEHP. After 4-5 weeks of treatment, all rats were sacrificed and the transplanted liver cells and portions of homotopic liver were processed for light and electron microscopy and for immunofluorescence microscopy. Morphometric analysis of transplanted hepatocytes showed a ninefold and fivefold increase in the volume density of peroxisomes in ciprofibrate and DEHP-fed rats, respectively. Indirect immunofluorescence studies revealed a marked induction of peroxisome-associated enzymes. From these data it is concluded that hepatic peroxisome proliferators cross the blood aqueous humor barrier and the transplanted hepatocytes in the anterior chamber of the eye retain their ability to recognize and respond to peroxisome proliferators.