In vitro metabolism of benzene, toluene, and xylene in rat liver

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1985

OSTI ID:5742066

Pathiratne, A

A headspace gas chromatographic method was used to study the metabolism of benzene, toluene, and m-xylene in rat liver. Metabolism of benzene was lower than that of toluene, or m-xylene. Investigating metabolic rates of subcellular fractions, it was found that glutathione and glutathione S-transferase in the cytosol are involved in metabolism of benzene and toluene by microsomes. When both benzene and toluene are present in the incubation medium, they act as inhibitors of each others metabolism. Toluene and m-xylene metabolism were induced by the pretreatment of rats with phenobarbital (75 mg/kg), or 3-methylcholanthrene (25 mg/kg), or Aroclor 1254 (75 mg/kg) for 3 days, whereas benzene metabolism was not induced by all pretreatments. Another series of experiments was conducted to compare the effects of benzene, toluene, and xylene pretreatment on liver metabolism. In vivo metabolism of /sup 14/C-toluene and possible covalent binding of /sup 14/C-toluene to microsomes were also investigated. /sup 14/C-toluene when incubated with liver microsomes in the presence of a NADPH generating system formed benzylalcohol and cresols. Some of the radioactivity was covalently bound preferentially to microsomal proteins. The binding process required cytochrome P-450 dependent mixed function oxidases. This study suggests that toluene is metabolized to several reactive intermediates by liver microsomal enzymes and these metabolites are responsible for the covalent binding to macromolecules which represents a subcellular mechanism by which toluene may express its own in vivo toxicity.

• Research Organization: North Dakota State Univ., Fargo (USA)
• OSTI ID: 5742066
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKYLATED AROMATICS
ANIMALS
AROMATICS
BENZENE
BIOCHEMICAL REACTION KINETICS
BODY
CARBON 14 COMPOUNDS
CELL CONSTITUENTS
COMPARATIVE EVALUATIONS
COVALENCE
CYTOCHROMES
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HYDROCARBONS
IN VITRO
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LIVER
MAMMALS
METABOLISM
METABOLITES
MICROSOMES
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PIGMENTS
PROTEINS
RATS
REACTION KINETICS
RODENTS
TOLUENE
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES
XYLENES