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. F urthermore, TCE end-stage metabolites, trichloroacetic acid and dichlo roacetic acid, cause lipid peroxidation in mouse liver. The time cours es of lipid peroxidation, free radical generation, and 8-hydroxydeoxyg uanosine (8OHdG) formation were used to assess the level of oxidative stress in the liver of B6C3F1 mice dosed orally once daily, 5 days a w eek for g weeks at 0, 400, 800, and 1200 mg/kg TCE in corn oil. Peroxi somal 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 el evated at the two highest dose levels of TCE on days 6 through 14 of t he study. 80HdG levels were statistically significant in the 1200 mg/k g/day group on days 2, 3, 10, 28, 49, and 56 only. The highest measure d free radical load, 307% of oil control, occurred at day 6. A signifi cant increase in cell and peroxisomal proliferation was observed durin g the same time period in the 1200 mg/kg/day group. Necrosis or an inc rease in apoptosis was not observed at any dose. The temporal relation ship 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 th e liver microenviromment which offers a selective advantage for certai n hepatocyte subpopulations.