Glutathione plus cytosol- and microsome-mediated binding of 1,2-dichloroethane to polynucleotides

Journal Article · Wed May 01 04:00:00 EDT 1985 · Toxicol. Appl. Pharmacol.; (United States)

DOI:https://doi.org/10.1016/0041-008X(85)90249-2· OSTI ID:6291156

Lin, E L; Mattox, J K; Pereira, M A

1,2-(1,2- UC)Dichloroethane was metabolized by rat hepatic microsomes to products that irreversibly bound polynucleotides. The polynucleotides were then enzymatically hydrolyzed and the products separated by a high-performance liquid chromatograph (HPLC) equipped with an ODS or a SCX column. The products of microsome-mediated binding were identified in the HPLC eluate as 1,N6-ethenoadenosine to polyadenylic acid, 3,N4-ethenocytidine to polycytidylic acid, and two cyclic derivatives to polyguanylic acid. 1,2-(1,2- UC)Dichloroethane was also metabolized in the presence of a glutathione (GSH)-cytosolic fraction and a polynucleotide. After enzymatic hydrolysis of the polynucleotide, the major peak of radioactivity was eluted from a Sephadex G-25 column in the salt volume which would exclude the presence of a product containing both GSH and a nucleoside. Chromatography by ODS-HPLC of the major peak from Sephadex G-25 indicated the presence of a GSH metabolite of 1,2-dichloroethane that did not contain a nucleoside. A similar hydrophilic peak was obtained for the hydrolysis products of polynucleotides from a glutathione plus cytosol incubation in which the polynucleotide instead of being added prior to the incubation was added after the incubation. In conclusion, covalently bound adducts were identified for microsome-mediated binding of 1,2-dichlorethane to polynucleotides, while no evidence was obtained for glutathione plus cytosol-mediated covalent binding to polynucleotides.

• Research Organization: US Environmental Protection Agency, Cincinnati, OH
• OSTI ID: 6291156
• Journal Information: Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 3; ISSN TXAPA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CHLORINATED ALIPHATIC HYDROCARBONS
CHROMATOGRAPHY
CONFIGURATION INTERACTION
CYTOPLASM
DECOMPOSITION
DRUGS
ENZYMATIC HYDROLYSIS
GLUTATHIONE
HALOGENATED ALIPHATIC HYDROCARBONS
HYDROLYSIS
IN VITRO
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LYSIS
MAMMALS
MICROSOMES
NUCLEOTIDES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANOIDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SEPARATION PROCESSES
SOLVOLYSIS
TRACER TECHNIQUES
VERTEBRATES