A subchronic exposure to trichloroethylene causes lipid peroxidation and hepatocellular proliferation in male B6C3F1 mouse liver.
The common groundwater contaminant trichloroethylene (TCE), when given by oral gavage, can produce free radical species during metabolism. Furthermore, TCE end-stage metabolites, trichloroacetic acid and dichloroacetic acid, cause lipid peroxidation in mouse liver. The time courses of lipid peroxidation, free radical generation, and 8-hydroxydeoxyguanosine (8OHdG) formation were used to assess the level of oxidative stress in the liver of B6C3F1 mice dosed orally once daily, 5 days a week for 8 weeks at 0, 400, 800, and 1200 mg/kg TCE in corn oil. Peroxisomal proliferation, cell proliferation, and apoptosis were evaluated at selected times during the study. Lipid peroxidation, as measured by thiobarbituric acid-reactive substances (TBARS), was significantly elevated at the two highest dose levels of TCE on days 6 through 14 of the study. 8OHdG levels were statistically significant in the 1200 mg/kg/day group on days 2, 3, 10, 28, 49, and 56 only. The highest measured free radical load, 307% of oil control, occurred at day 6. A significant increase in cell and peroxisomal proliferation was observed during the same time period in the 1200 mg/kg/day group. Necrosis or an increase in apoptosis was not observed at any dose. The temporal relationship between oxidative stress and cellular response of proliferation, both of which occur and resolve within the same relative time period, suggests that TCE-induced mitogenesis may result from alteration in the liver microenvironment which offers a selective advantage for certain hepatocyte subpopulations.
Toxicology Division, Armstrong Laboratory, Toledo, Ohio, USA.
S R
SR
Channel
J R
JR
Latendresse
J K
JK
Kidney
J H
JH
Grabau
J W
JW
Lane
L
L
Steel-Goodwin
M C
MC
Gothaus
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight; D002455:Cell Division / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D014241:Trichloroethylene / Q000494:pharmacology*
D005609:Free Radicals; D014241:Trichloroethylene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine