Quantitative Assessment of Peroxisome Proliferation in B6C3F1 Mouse Liver afterSubchronic Exposure to Trichloroethylene by Gavage

摘要

Trichioroethylene (TCE), an industrial solvent and common groundwatercontaminant, is hepatocarcinogenic in mice when given at high doses. In this study, groups of mice were orally administered water, corn oil, or TCE (400, 800, 1200 mg/kg) in corn oil in equal volumes for 8 weeks (once/day, 5 days/week). We present data showing significant induction of mRNA levels for cytochrome P450 4A1 in high dose groups (3-30 times control) and glyceraldehyde-3-phosphate dehydrogenase (1.4-3.4 times control), as determined by Northern analysis throughout the study. The induction of these genes is closely associated with peroxisome proliferation. In addition, gamma-glutamylcysteine synthetase mRNA displayed elevations in high dose groups (1.3 to 3.6 times control). The implication of peroxisome proliferation was verified by TEM examination and quantitation of peroxisome numbers. The evidence of peroxisome proliferation-associated gene induction throughout the 56-day exposures suggests that peroxisome proliferation could play a continuing role in the biological effects of a longer-term TCE exposure.