Biochemical, histological, and ultrastructural changes in rat and mouse liver following the administration of trichloroethylene: possible relevance to species differences in hepatocarcinogenicity.
Trichloroethylene (TRI), administered by gavage for 10 consecutive days, at doses of 500 to 1500 mg/kg body wt increased liver weight (175% of control), decreased hepatic DNA concentration (66% of control), and increased the synthesis of DNA (500% of control; as measured by [3H]dT incorporation) in B6C3F1 mice and Alderley Park mice. Similar treatment of Osborne-Mendel rats or Alderley Park rats resulted in smaller increases in liver weight (130% of control) and decreases in DNA concentration (83% of control). No effect of TRI on DNA synthesis was seen in rats. The increased DNA synthesis in the mouse was not apparently due to regenerative hyperplasia since no signs of necrosis were seen. Furthermore the increased [3H]dT incorporation probably represented semiconservative replication of DNA and not repair, since a parallel increase of mitotic figures was observed. Hence, the liver growth noted after TRI administration appears to be due to liver cell enlargement (hypertrophy) in the rat, but both hypertrophy and hyperplasia (cell proliferation) in the mouse. An important observation has been that TRI induced the peroxisomal enzyme activities, catalase, and cyanide-insensitive palmitoyl-CoA oxidation (147 and 786% of control, respectively), in mice but not in rats. Furthermore, increases in peroxisome volume density (up to 1110% of control) were observed in mice receiving TRI. These observations lead us to suggest that the species difference in hepatocarcinogenicity of TRI, seen between the rat and mouse, is possibly due to a species difference in peroxisome proliferation and cell proliferation, the peroxisome proliferation leading to increased reactive oxygen species and DNA damage, and the cell proliferation then acting to promote this lesion.
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008830:Microbodies / Q000187:drug effects; D008854:Microscopy, Electron; D051381:Rats; D013045:Species Specificity; D014241:Trichloroethylene / Q000494:pharmacology*
D002273:Carcinogens; D014241:Trichloroethylene; D004247:DNA