DNA methylation in rat liver by daminozide, 1,1-dimethylhydrazine, and dimethylnitrosamine
(methyl-/sup 14/C)Daminozide (succinic acid 2',2'-dimethylhydrazide; 37 mg/kg), 1,1-(/sup 14/C)dimethylhydrazine (UDMH; 19 mg/kg), and (/sup 14/C)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-/sup 3/H)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.
- Research Organization:
- Institute of Toxicology, Schwerzenbach (Switzerland)
- OSTI ID:
- 6071477
- Journal Information:
- Fundam. Appl. Toxicol.; (United States), Journal Name: Fundam. Appl. Toxicol.; (United States) Vol. 11:4; ISSN FAATD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CHEMICAL REACTIONS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DNA
GLANDS
HYDRAZINE
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
METHYLATION
NITROGEN COMPOUNDS
NITROSAMINES
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PLANT GROWTH REGULATORS
RATS
RODENTS
SEPARATION PROCESSES
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES