Advertisement

Urinary Metabolites of Benzene in the Mouse

  • Stephen L. Longacre
  • James J. Kocsis
  • Charlotte M. Witmer
  • Robert Snyder
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Abstract

Chronic benzene toxicity, which is characterized by decreases in circulating blood cell levels due to depression of the bone marrow, is thought to be caused by a metabolite of benzene. Our understanding of the metabolism of benzene derives largely from the reports of R.T. Williams and his co-workers (Porteus and Williams, 1949a, 1949b; Parke and Williams, 1952, 1953a, 1953b), who were the first to systematically identify benzene metabolites in rabbit urine after administering benzene to rabbits. Forty-five percent of the administered benzene was recovered. in the expired air, 43% of the administered dose being unchanged benzene and the remaining 2% was carbon dioxide. Urine contained 35% of the administered radioactivity, mostly in the form of conjugated phenolic metabolites of benzene. Upon acid hydrolysis of the conjugates, phenol was found to account for 24% of the dose while other metabolites included catechol (2.2%), hydroquinone (4.8%), and hydroxyhydroquinone (0.3%). 1-Phenylmercapturic acid (0.5%) and trans-trans-muconic (1.3%) acid were also recovered in the urine.

Keywords

High Pressure Liquid Chromatography Urinary Metabolite Mercapturic Acid Incubation Product Free Phenol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Bibliography

  1. Andrews, L.S., Lee, E.W., Witmer, C.M., Kocsis, J.J. and Snyder, R. Effects of toluene on the metabolism, disposition and hemopoietic toxicity of H benzene. Biochem. Pharmacol. 26, 293–300 (1977).PubMedCrossRefGoogle Scholar
  2. Behringer, V.M. and Fackler, E. Eine einfache Synthese der race-mischen Mercaptursauren. Justus Liebigs Ann. Chem. 564 band, 73–78 (1949).CrossRefGoogle Scholar
  3. Dustin, P., Jr. The action of mitotic poisons on normal and pathological blood cell formation. Sang 21, 299–330 (1950).Google Scholar
  4. Gonasun, L.M., Witmer, C., Kocsis, J.J. and Snyder, R. Benzene metabolism in mouse liver microsomes. Toxicol. Appl. Pharmacol. 26, 398–406 (1973).CrossRefGoogle Scholar
  5. Jerina, D.M. and Daly, J.W. Arene oxides: A. new aspect of drug metabolism. Metabolic formation of arene oxides explains many toxic and carcinogenic properties of aromatic hydrocarbons. Science 184, 573–582 (1974).CrossRefGoogle Scholar
  6. Jerina, D., Daly, J., Witkop, B., Zaltzman-Nirenberg, P. and Udenfriend, S. Role of the arene oxide-oxepin system in the metabolism of aromatic substrates. L. In vitro converson of benzene oxide to a premercapturic acid and a dihydrodiol. Archiv. Biochem. Biophys. 128, 176–183 (1968).CrossRefGoogle Scholar
  7. Parke, D.V. and Williams, R.T. Studies in Detoxication 44. The metabolism of benzene. The muconic acid excreted by rabbits receiving benzene. Determination of the isomeric muconic acids. Biochem. J. 51, 339–348 (1952).PubMedGoogle Scholar
  8. Parke, D.V. and Williams, R.T. Studies in Detoxication 49. The metabolism of benzene containing 14C-benzene. Biochem. J. 54, 231–238 (1953a).PubMedGoogle Scholar
  9. Parke, D.V. and Williams, R.T. Studies in Detoxication 54. The metabolism of benzene (1). The formation of phenylglucuronide and phen jsulphuric acid from 14C-benzene. (b) The metabolism of 14C-phenol. Biochem. J. 55, 337–340 (1953b).PubMedGoogle Scholar
  10. Porteous, J.W. and Williams, R.T. Studies in Detoxication 19. The metabolism of benzene. Ia. The determination of phenol in urine with 2,6-dihydroquinonecinloroimide. b. The excretion of phenol, glucuronic acid and ethereal sulphates by rabbits receiving benzene and phenol. c. Observations on the determination of catechol, quinol and muconic acid in urine. Biochem. J. 44, 46–55 (1949a).Google Scholar
  11. Porteous, J.W. and Williams, R.T. Studies in Detoxication 20. The metabolism of benzene. H. The isolation of phenol, catechol, quinol and hydroxyquinol from the ethereal sulphate fraction of the urine of rabbits receiving benzene orally. Biochem. J. 44, 56–61 (1949b).Google Scholar
  12. Sato, T., Fukuyama, T., Suzuki, T. and Yoshikawa, H. 1,2 Dihydro-1,2-dihydroxybenzene and several other substances in the metabolism of benzene. J. Biochemistry 53, 23–27 (1963).Google Scholar
  13. Snyder, R., Longacre, S.L., Witmer, C.M. and Kocsis, J.J., Metabolic correlates of benzene toxicity in: Biological Reactive Intermediates: Chemical Mechanisms and Biological Effects, Snyder, R., Parke, D.V., Kocsis, J.J., Jollow, D.J. and Gibson, G., (eds) Plenum Publishing Co., N.Y. (1981).Google Scholar
  14. Tunek, A., Platt, K.L., Bentley, P. and Oesch, F. Microsomal metabolism of benzene to species irreversibly binding to microsomal protein and effects of modification of this metabolism. Mol. Pharmacol. 14, 920–929 (1978).PubMedGoogle Scholar
  15. Zbarsky, S.M. and Young, L. Mercapturic acids I. The synthesis of phenyl-1-cysteine and 1-phenylmercapturic acid. J. Biol. Chem. 151, 487–492 (1943).Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Stephen L. Longacre
    • 1
  • James J. Kocsis
    • 1
  • Charlotte M. Witmer
    • 1
  • Robert Snyder
    • 1
  1. 1.Thomas Jefferson UniversityUSA

Personalised recommendations