S-adenosylmethionine metabolism and DNA methylation in hydrazine-treated rats

Journal Article · Sat Jan 01 04:00:00 EST 1983 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/4.8.953· OSTI ID:5684113

Barrows, L R; Shank, R C; Magee, P N

The treatment of rats with hepatotoxic doses of hydrazine (NH2-NH2) induces the rapid formation of 7-methylguanine and O6-methylguanine in liver DNA. The methyl moiety in these reactions might be derived from the cellular S-adenosylmethionine pool because radioactivity administered to these rats as methionine rapidly appears in the DNA as methylated guanine. An increased incorporation of radioactivity into 5-methylcytosine was previously reported followed by subsequent suppression. This increased radiolabeling of 5-methylcytosine coincided with time of maximal DNA guanine methylation. To determine the nature of S-adenosylmethionine metabolism during the period of DNA methylation induced by hydrazine treatment, and to determine if the increased radiolabeling of 5-methylcytosine at this time reflected an actual increase in 5-methylcytosine synthesis, liver DNA synthesis and S-adenosylmethionine levels and turnover were assayed. Liver S-adenosylmethionine concentrations varied slightly between control rats and hydrazinetreated rats during the first five hours after hydrazine administration, and no difference was detectable in the incorporation of administered (3H)methionine into S-adenosylmethionine. Because S-adenosylmethionine specific radioactivity in hydrazine-treated rats was not different from control rats, the previously observed increased radiolabeling of 5-methylcytosine appeared to represent an actual increase in synthesis. This conclusion was supported by finding that incorporation of radioactive thymidine into DNA was also accelerated immediately following hydrazine administration, again followed by a decrease. 5-Methylcytosine sythesis, therefore, appears to follow DNA synthesis during hydrazine toxicity, and formation of 7-methylguanine and O6-methylguanine in liver DNA of hydrazine-treated rats occurs during a short period of increased DNA sythesis and 5-methylcytosine formation very early in hydrazine toxicity.

• Research Organization: Fels Research Institute, Temple University, School of Medicine, Philadelphia, PA
• OSTI ID: 5684113
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 4:8; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AMINO ACIDS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CYTOSINE
DNA
DNA REPLICATION
DRUGS
GUANINE
HETEROCYCLIC COMPOUNDS
HYDRAZINE
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
METABOLISM
METHIONINE
METHYLATION
NITROGEN COMPOUNDS
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PURINES
PYRIMIDINES
RATS
RODENTS
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES