c-H-ras and c-K-ras gene hypomethylation in the livers and hepatomas of rats fed methyl-deficient, amino acid-defined diets. 1988

M R Bhave, and M J Wilson, and L A Poirier
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research Facility, MD 21701.

The extent of methylation of the c-H-ras and c-K-ras oncogenes was compared in neoplastic and preneoplastic livers of rats fed one of several methyl-deficient, amino acid-defined diets for 18 months, with or without a preceding initiating dose of diethylnitrosamine (DEN). The restriction endonucleases MspI, HpaII, HhaI, PaeR71 and XhoI were used for studying the extent and pattern of DNA methylation. The results indicated that both c-H-ras and c-K-ras oncogenes were hypomethylated in all DNA samples derived from both neoplastic and preneoplastic livers of rats fed any of the methyl-deficient diets used, regardless of whether or not the rats had received an initiating dose of DEN. It thus appears that dietary methyl deficiency does indeed lead to hypomethylation of ras genes in the DNAs of the resulting tumors. However, the significance of this hypomethylation in the tumorigenic process is not clearly understood.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008114 Liver Neoplasms, Experimental Experimentally induced tumors of the LIVER. Hepatoma, Experimental,Hepatoma, Morris,Hepatoma, Novikoff,Experimental Hepatoma,Experimental Hepatomas,Experimental Liver Neoplasms,Hepatomas, Experimental,Neoplasms, Experimental Liver,Experimental Liver Neoplasm,Liver Neoplasm, Experimental,Morris Hepatoma,Novikoff Hepatoma
D008297 Male Males
D008745 Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed) Methylations
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D011230 Precancerous Conditions Pathological conditions that tend eventually to become malignant. Preneoplastic Conditions,Condition, Preneoplastic,Conditions, Preneoplastic,Preneoplastic Condition,Condition, Precancerous,Conditions, Precancerous,Precancerous Condition
D011519 Proto-Oncogenes Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc. Proto-Oncogene,Proto Oncogene,Proto Oncogenes
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D004032 Diet Regular course of eating and drinking adopted by a person or animal. Diets
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

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