A Subchronic Exposure to Trichloroethylene Causes Lipid Peroxidation and Hepatocellular Proliferation in Male B6C3F1 Mouse Liver

Abstract

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.

Evaluation of Hepatoprotective and Anticancer Properties of Aqueous Olive Leaf Extract in Chemically Induced Hepatocellular Carcinoma in Rats

“…Rats were given TCA by gavage as 500mg/kg once a day for 5 days [31]. TCA was chosen because it has been reported to increase liver growth, cell proliferation, and lipid peroxidation in mice [32][33][34][35]. All other chemicals used are of analytical grade obtained from Sigma (USA).…”

Effects of Trichloroethylene on p53 and Bcl-2 Expression, Chromosome Loss and Catalase Activity Inhibition in Human

“…17 TCE and its metabolites have been reported to decrease the methylation of promoter regions of the c-Myc gene, leading to an increased mRNA expression in the liver of B6C3F1 mice. 15,18,19 In this study, TCE effected lymphocyte viability and chromosome loss. The numbers of living lymphocytes were reduced when the TCE concentrations increased and chromosome loss was found.…”

Biochemical effects of chloral hydrate on male rats following 7-day drinking water exposure

“…Another possible explanation is that the body is able to respond to and accommodate the peroxidative change with time. Thus, Channel et al 38 observed, when male mice were treated with trichloroethylene (800 and 1200 mg kg Ϫ1 day Ϫ1 ) for 8 weeks, that their hepatic TBARS were significantly elevated on days 6-14 but returned to control levels by the end of the treatment period. In the present study, the elevated hepatic GST activity and glutathione level in the high-dose group provided some indications that the liver was indeed responding to CH exposure by increasing its phase II drug metabolizing capacity and the level of one of its major endogenous antioxidants.…”