Abstract
Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are mouse liver carcinogens. Methylation of the c-jun and c-myc genes, expression of both genes and DNA methyltransferase (DNA MTase) activity were determined in liver tumors initiated by N-methyl-N-nitrosourea and promoted by DCA and TCA in female B6C3F1 mice. Hypomethylated and over-expression of c-jun and c-myc genes were found in DCA- and TCA-promoted liver tumors. DNA MTase activity was increased in tumors while decreased in non-involved liver. Thus, DCA- and TCA-promoted carcinogenesis appears to include decreased methylation and increased expression of c-jun and c-myc genes in the presence of increased DNA MTase activity.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Alkylating Agents / toxicity
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Animals
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Blotting, Northern
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Blotting, Southern
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Blotting, Western
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DNA Methylation / drug effects
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DNA, Neoplasm / genetics
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DNA, Neoplasm / metabolism
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Dichloroacetic Acid / administration & dosage*
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Liver Neoplasms, Experimental / chemically induced
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Liver Neoplasms, Experimental / genetics*
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Liver Neoplasms, Experimental / metabolism
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Methylnitrosourea / toxicity
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Methyltransferases / drug effects*
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Methyltransferases / metabolism
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Mice
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-jun / genetics*
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Proto-Oncogene Proteins c-jun / metabolism
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Proto-Oncogene Proteins c-myc / genetics*
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Proto-Oncogene Proteins c-myc / metabolism
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Trichloroacetic Acid / administration & dosage*
Substances
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Alkylating Agents
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DNA, Neoplasm
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Proto-Oncogene Proteins c-jun
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Proto-Oncogene Proteins c-myc
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RNA, Messenger
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Trichloroacetic Acid
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Methylnitrosourea
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Dichloroacetic Acid
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Methyltransferases