Extra-hepatic gsh-dependent metabolism of 1,2-dibromoethane (dbe) and 1,2-dibromo-3-chloropropane (dbcp) IN the rat and mouse

R. T. Macfarland, A Jay Gandolfi, I. G. Sipes

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23 Citations (Scopus)

Abstract

Although DBE is metabolized by both microsomal and cytosolic pathways, it is the latter, GSH-dependent route, that may lead to hepatic and extra-hepatic genotoxicity and mutagenicity. As both DBE and DBCP exhibit predominantly extra-hepatic toxicity, their in vitro GSH-dependent debromination was measured in cytosolic fractions prepared from liver, kidney, testes and stomachs of Sprague-Dawley rats and Swiss-Webster mice. There was a marked species difference between the rat and mouse, vith the rat metabolizing DBCP more rapidly than DBE, and the mouse metabolizing DBE more rapidly than DBCP. Hepatic rates exceeded those seen in extra-hepatic tissues in every case. Extra-hepatic rates of debromination represented as much as 84% of the hepatic rates, and generally followed the order: kidney > testes > stomach. Rates of metabolism for DBE and DBCP represented only a small fraction of the total cytosolic GSH S-transferase activity. These findings suggest significant levels of GSH-dependent metabolism may occur within those tissues associated with the in vivo toxicity of DBE and DBCP.

Original languageEnglish (US)
Pages (from-to)213-227
Number of pages15
JournalDrug and Chemical Toxicology
Volume7
Issue number3
DOIs
StatePublished - 1984

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Ethylene Dibromide
Metabolism
Rats
Toxicity
Liver
Tissue
Testis
Stomach
Transferases
Kidney
1,2-dibromo-3-chloropropane
Sprague Dawley Rats

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health
  • Chemical Health and Safety
  • Chemistry(all)

Cite this

Extra-hepatic gsh-dependent metabolism of 1,2-dibromoethane (dbe) and 1,2-dibromo-3-chloropropane (dbcp) IN the rat and mouse. / Macfarland, R. T.; Gandolfi, A Jay; Sipes, I. G.

In: Drug and Chemical Toxicology, Vol. 7, No. 3, 1984, p. 213-227.

Research output: Contribution to journalArticle

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N2 - Although DBE is metabolized by both microsomal and cytosolic pathways, it is the latter, GSH-dependent route, that may lead to hepatic and extra-hepatic genotoxicity and mutagenicity. As both DBE and DBCP exhibit predominantly extra-hepatic toxicity, their in vitro GSH-dependent debromination was measured in cytosolic fractions prepared from liver, kidney, testes and stomachs of Sprague-Dawley rats and Swiss-Webster mice. There was a marked species difference between the rat and mouse, vith the rat metabolizing DBCP more rapidly than DBE, and the mouse metabolizing DBE more rapidly than DBCP. Hepatic rates exceeded those seen in extra-hepatic tissues in every case. Extra-hepatic rates of debromination represented as much as 84% of the hepatic rates, and generally followed the order: kidney > testes > stomach. Rates of metabolism for DBE and DBCP represented only a small fraction of the total cytosolic GSH S-transferase activity. These findings suggest significant levels of GSH-dependent metabolism may occur within those tissues associated with the in vivo toxicity of DBE and DBCP.

AB - Although DBE is metabolized by both microsomal and cytosolic pathways, it is the latter, GSH-dependent route, that may lead to hepatic and extra-hepatic genotoxicity and mutagenicity. As both DBE and DBCP exhibit predominantly extra-hepatic toxicity, their in vitro GSH-dependent debromination was measured in cytosolic fractions prepared from liver, kidney, testes and stomachs of Sprague-Dawley rats and Swiss-Webster mice. There was a marked species difference between the rat and mouse, vith the rat metabolizing DBCP more rapidly than DBE, and the mouse metabolizing DBE more rapidly than DBCP. Hepatic rates exceeded those seen in extra-hepatic tissues in every case. Extra-hepatic rates of debromination represented as much as 84% of the hepatic rates, and generally followed the order: kidney > testes > stomach. Rates of metabolism for DBE and DBCP represented only a small fraction of the total cytosolic GSH S-transferase activity. These findings suggest significant levels of GSH-dependent metabolism may occur within those tissues associated with the in vivo toxicity of DBE and DBCP.

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