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 for up to 4 days gave rise to hepatomegaly resulting from a combination of hepatocyte hyperplasia, mainly in the periportal region of the lobule, and centrilobular cell hypertrophy. In hepatocytes undergoing mitosis there was a redistribution of dense vesicles and some peroxisomes to the perinuclear region of the cytoplasm. With increasing length of 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 glutathione-S transferase B, C and E showed a dramatic reduction and redistribution of those enzymes in mitotic cells and their absence in the region of the chromosomes. These events may increase the vulnerability of DNA to damage in specific cells.
Soames
A R
AR
Pathology Section, Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, UK.
Foster
J R
JR
D000818:Animals; D002875:Chromosomes / Q000187:drug effects*; D002992:Clofenapate / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006529:Hepatomegaly / Q000139:chemically induced / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008830:Microbodies / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008938:Mitosis / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D002992:Clofenapate; D005982:Glutathione Transferase