DNA methylation in rat liver by daminozide, 1,1-dimethylhydrazine, and dimethylnitrosamine. 1988

P Sagelsdorff, and W K Lutz, and C Schlatter
Institute of Toxicology, Swiss Federal Institute of Technology, Schwerzenbach.

[methyl-14C]Daminozide (succinic acid 2',2'-dimethylhydrazide; 37 mg/kg), 1,1-[14C]dimethylhydrazine (UDMH; 19 mg/kg), and [14C]dimethylnitrosamine (DMNA; 0.1 mg/kg) were administered by oral gavage to male Sprague-Dawley rats. After 24 hr, the animals were killed and DNA was purified from the livers to constant specific radioactivity. After enzymatic degradation of the DNA to the 3'-deoxynucleotides the level of DNA methylation was determined by HPLC analysis. Radiolabeled 7-methylguanine (7mG) was identified by cochromatography with unlabeled 7mG added as standard after acidic depurination of DNA and HPLC analysis of purines and apurinic acid. All three compounds were found to methylate DNA. The relative potencies were 1:47:4900 for daminozide:UDMH:DMNA. With [methyl-3H]UDMH, the formation of 7mG was investigated as a function of dose administered, at 20, 2, and 0.2 mg/kg. The methylation of DNA was strictly proportional to the dose. The data were used to compare the level of DNA alkylation derived from residues of daminozide and UDMH in treated apple with the genotoxicity of the intake of N-nitroso compounds in Germany and Japan. It is estimated that these residues could lead to a DNA methylation in the liver of about 6% of an average exposure to DMNA.

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
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
D008763 Methylhydrazines Hydrazines substituted by one or more methyl groups in any position.
D009152 Mutagenicity Tests Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests. Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D010937 Plant Growth Regulators Any of the hormones produced naturally in plants and active in controlling growth and other functions. There are three primary classes: auxins, cytokinins, and gibberellins. Phytohormone,Phytohormones,Plant Growth Regulator,Plant Hormone,Plant Hormones,Growth Regulators, Plant,Regulators, Plant Growth,Growth Regulator, Plant,Hormone, Plant,Hormones, Plant,Regulator, Plant Growth
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004127 Dimethylhydrazines Hydrazines substituted with two methyl groups in any position. Dimethylhydrazine

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