Quantitative Assessment of Peroxisome Proliferation in B6C3F1 Mouse Liver after Subchronic Exposure to Trichloroethylene by Gavage.
Interim rept. Jul 94-Nov 96,
MANTECH GEO-CENTERS JOINT VENTURE DAYTO OH
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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 mgkg in corn oil in equal volumes for 8 weeks onceday, 5 daysweek. 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.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Physical Chemistry