JUXTAPOSITION OF PEROXISOMES AND CHROMOSOMES IN MITOTIC HEPATOCYTES FOLLOWING METHYL CLOFENAPATE ADMINISTRATION TO RATS

Administration of 25 mg/kg/day methyl clofenapate to Alpk/APfSD rats f or up to 4 days gave rise to hepatomegaly resulting from a combination of hepatocyte hyperplasia, mainly in the periportal region of the lob ule, and centrilobular cell hypertrophy. In hepatocytes undergoing mit osis there was a redistribution of dense vesicles' and some peroxisome s to the perinuclear region of the cytoplasm. With increasing length o f exposure to methyl clofenapate the number of peroxisomes located in this region during mitosis increased. Chromosomes observed by electron microscopy were seen to lie in close apposition to these organelles. Immunocytochemical localization of the Phase II conjugating enzymes gl utathione-S transferase B, C and E showed a dramatic reduction and red istribution of those enzymes in mitotic cells and their absence in the region of the chromosomes. These events may increase the vulnerabilit y of DNA to damage in specific cells.