Effect of trichloroethylene on DNA methylation and expression of early-intermediate protooncogenes in the liver of B6C3F1 mice.
Trichloroethylene (TCE) is a multimedia environmental pollution that is carcinogenic in mouse liver. The ability of TCE to modulate DNA methylation and the expression of immediate-early protooncogenes was evaluated. Female B6C3F1 mice were administered 1000 mg/kg TCE by gavage 5 days/week and killed after 5, 12, or 33 days of exposure. Methylation of DNA as 5-methylcytosine was decreased by 5 days of treatment with TCE and remained reduced for 33 days. TCE also decreased the methylation of the promoter regions for the protooncogenes, c-jun and c-myc. The expression of the mRNA for the two protooncogenes was increased between 60 and 120 minutes after administering the last dose of TCE and returned to control level by 24 hours. The expression of the mRNA for c-fos remained undetectable after administering TCE. Hence, TCE decreased the methylation both of total DNA and the promoters for the c-jun and c-myc genes and increased the expression of their mRNA. The decreased methylation and increased expression of the two immediate-early protooncogenes might be associated with TCE-induced increase in cell proliferation and promotion of tumors.
Department of Pathology, Medical College of Ohio, Toledo 43614, USA.
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Tao
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Ge
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Xie
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Kramer
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Pereira
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012997:Solvents / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*
D004785:Environmental Pollutants; D017874:Immediate-Early Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012997:Solvents; D014241:Trichloroethylene; D004247:DNA