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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1994-5-4
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pubmed:abstractText |
The liver tumor-prone B6C3F1 mouse (C57Bl/6 female x C3H/He male), in conjunction with the more susceptible C3H/He paternal strain and the resistant C57BL/6 maternal strain, is an excellent model for studying the mechanisms involved in carcinogenesis. The study reported here indicated that the B6C3F1 mouse inherited a maternal raf allele containing a methylated site not present in the paternal allele. Seven days after partial hepatectomy or after administration of a promoting dose of phenobarbital (PB) for 14 d; raf in B6C3F1 mouse liver was hypomethylated. The additional methylated site in the allele inherited from C57BL/6 was not maintained. The methylation status of raf in the liver of the C57BL/6 mouse was not affected by PB treatment. This indicates that the B6C3F1 mouse is less capable of maintaining methylation of raf than the C57BL/6 strain is. In both PB-induced and spontaneous B6C3F1 liver tumors, raf was hypomethylated in a nonrandom fashion. The level of raf mRNA increased in seven of 10 PB-induced tumors but in only one of five spontaneous tumors, whereas the level of Ha-ras mRNA increased in nine of 10 PB-induced tumors and in four of five spontaneous tumors. The results of our investigation (a) support the hypothesis that hypomethylation of DNA is a nongenotoxic mechanism involved in tumorigenesis, (b) support the notion that PB promotes liver tumors that develop along a pathway different from that leading to spontaneous tumors, and (c) indicate that differences in DNA methylation between C57BL/6 and B6C3F1 mice could, in part, account for the unusually high tendency of the latter strain to develop liver tumors.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0899-1987
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
9
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pubmed:geneSymbol |
raf,
ras
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
155-66
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pubmed:dateRevised |
2011-10-27
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pubmed:meshHeading |
pubmed-meshheading:7908202-Animals,
pubmed-meshheading:7908202-Cell Division,
pubmed-meshheading:7908202-Female,
pubmed-meshheading:7908202-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:7908202-Genes, ras,
pubmed-meshheading:7908202-Liver Neoplasms,
pubmed-meshheading:7908202-Male,
pubmed-meshheading:7908202-Methylation,
pubmed-meshheading:7908202-Mice,
pubmed-meshheading:7908202-Mice, Inbred C3H,
pubmed-meshheading:7908202-Mice, Inbred C57BL,
pubmed-meshheading:7908202-Oncogenes,
pubmed-meshheading:7908202-Phenobarbital,
pubmed-meshheading:7908202-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:7908202-Proto-Oncogene Proteins,
pubmed-meshheading:7908202-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:7908202-RNA, Messenger
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pubmed:year |
1994
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pubmed:articleTitle |
Alterations in the methylation status and expression of the raf oncogene in phenobarbital-induced and spontaneous B6C3F1 mouse liver tumors.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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