Hypomethylation and overexpression of c-jun and c-myc protooncogenes and increased DNA methyltransferase activity in dichloroacetic and trichloroacetic acid-promoted mouse liver tumors.
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.
Tao
L
L
Department of Pathology, Medical College of Ohio, Health Education Building, 3055 Arlington Ave., Toledo, OH 43614-5806, USA. ltao@mco.edu
Yang
S
S
Xie
M
M
Kramer
P M
PM
Pereira
M A
MA
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D003999:Dichloroacetic Acid / Q000008:administration & dosage*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008770:Methylnitrosourea / Q000633:toxicity; D008780:Methyltransferases / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014238:Trichloroacetic Acid / Q000008:administration & dosage*
D000477:Alkylating Agents; D004273:DNA, Neoplasm; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014238:Trichloroacetic Acid; D008770:Methylnitrosourea; D003999:Dichloroacetic Acid; D008780:Methyltransferases