Deuterium isotope effect on the metabolism and toxicity of 1,2-dibromoethane

Journal Article · Thu Jun 30 04:00:00 EDT 1983 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(83)90297-1· OSTI ID:5589983

White, R D; Gandolfi, A J; Bowden, G T; Sipes, I G

The metabolism, hepatotoxicity, and hepatic DNA damage of 1,2-dibromoethane (EDB) and tetradeutero-1,2-dibromoethane (d4EDB) were compared in male Swiss-Webster mice. In vitro studies that measured bromide ion released from the substrate to monitor the rate of metabolism showed that the hepatic microsomal metabolism of EDB was significantly reduced by deuterium substitution, while metabolism by the hepatic glutathione S-transferases was unaffected. Three hours after ip administration of EDB or d4EDB (50 mg/kg), there was 42% less bromide in the plasma of d4EDB-treated mice than in the plasma of EDB-treated mice. This difference demonstrates a significant deuterium isotope effect on the metabolism of EDB in vivo. Although the metabolism of d4EDB was less than that of EDB 3 hr after exposure, the DNA damage caused by both analogs was not significantly different at this time point. At later time points (8, 24, and 72 hr), d4EDB caused significantly greater DNA damage than EDB. Since the decreased metabolism of d4EDB was apparently due to a reduced rate of microsomal oxidation, these data support the hypothesis that conjugation with GSH is responsible for the genotoxic effects of EDB.

• Research Organization: Department of Pharmacology and Toxicology, Arizona Health Sciences Center, University of Arizona, Tucson
• OSTI ID: 5589983
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 69:2; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BODY
CELL CONSTITUENTS
DEUTERIUM
DEUTERIUM COMPOUNDS
DIGESTIVE SYSTEM
DNA
GENETIC EFFECTS
GLANDS
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
ISOTOPE EFFECTS
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
METABOLISM
MICE
MICROSOMES
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
ORGANS
RODENTS
STABLE ISOTOPES
TIME DEPENDENCE
TOXICITY
VERTEBRATES