Urinary Metabolites of Benzene in the Mouse
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.
KeywordsHigh Pressure Liquid Chromatography Urinary Metabolite Mercapturic Acid Incubation Product Free Phenol
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- Dustin, P., Jr. The action of mitotic poisons on normal and pathological blood cell formation. Sang 21, 299–330 (1950).Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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