Quantitative Assessment of Peroxisome Proliferation in B6C3F1 Mouse Liver after Subchronic Exposure to Trichloroethylene by Gavage.
Abstract
Trichioroethylene (TCE), an industrial solvent and common groundwater contaminant, is hepatocarcinogenic in mice when given at high doses. One potential mechanism for TCE-induced liver tumors is the formation of excessive reactive oxygen species during lipid peroxidation. As reported in previous studies by analysis of protein levels, enzyme activity or transmission electron microscopy (TEM) examination of liver tissue, TCE exposure results in peroxisome proliferation. 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1997
- Accession Number
- ADA327962
Entities
People
- Gia M. Randall
- John H. Grabau
- John R. Latendresse
- John W. Lane
- Kevin T. Geiss