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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Nov;83(21):8356–8360. doi: 10.1073/pnas.83.21.8356

Formation of muconaldehyde, an open-ring metabolite of benzene, in mouse liver microsomes: an additional pathway for toxic metabolites.

L Latriano, B D Goldstein, G Witz
PMCID: PMC386927  PMID: 3464956

Abstract

It has been proposed that a ring-opened form may be responsible for the toxicity of benzene. The present studies demonstrate that incubation of [14C]benzene with liver microsomes (obtained from male CD-1 mice treated with benzene) in the presence of NADPH results in the formation of a ring-opened product. Evidence for the identity of this product was obtained by derivatizing with 2-thiobarbituric acid (TBA), which resulted in the formation of an adduct with a 490-nm absorbance maximum. This maximum is identical to that observed after authentic trans,trans-muconaldehyde has reacted with TBA. Separation of muconaldehyde, both with and without trapping with TBA, from other benzene metabolites in the incubation mixture was accomplished by HPLC. The radioactivity profile of fractions collected during HPLC analysis contained peaks that eluted with muconaldehyde and the muconaldehyde-TBA adduct. The structure of the ring-opened product was confirmed by mass spectrometry, studies in which the HPLC peak from the microsomal incubation mixture that eluted at the retention time of authentic muconaldehyde was collected and derivatized with 2,4-dinitrophenylhydrazine. The high-resolution mass spectrum of this sample contained an ion with an m/z of 291.0729, corresponding to muconaldehyde mono-dinitrophenylhydrazone. These results indicate that benzene is metabolized in vitro to a ring-opened product identified as muconaldehyde.

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Selected References

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  1. Cohen G., Cederbaum A. I. Chemical evidence for production of hydroxyl radicals during microsomal electron transfer. Science. 1979 Apr 6;204(4388):66–68. doi: 10.1126/science.432627. [DOI] [PubMed] [Google Scholar]
  2. Dowty B. J., Brightwell N. E., Laseter J. L., Griffin G. W. Dye-sensitized photooxidation of phenanthrene. Biochem Biophys Res Commun. 1974 Mar 25;57(2):452–456. doi: 10.1016/0006-291x(74)90952-8. [DOI] [PubMed] [Google Scholar]
  3. Gad-El Karim M. M., Ramanujam V. M., Legator M. S. trans,trans-Muconic acid, an open-chain urinary metabolite of benzene in mice. Quantification by high-pressure liquid chromatography. Xenobiotica. 1985 Mar;15(3):211–220. doi: 10.3109/00498258509045351. [DOI] [PubMed] [Google Scholar]
  4. Goldstein B. D. Benzene toxicity: a critical evaluation: hematotoxicity in humans. J Toxicol Environ Health Suppl. 1977;2:69–105. [PubMed] [Google Scholar]
  5. HORIGUCHI M., KANDATSU M. Isolation of 2-aminoethane phosphonic acid from rumen protozoa. Nature. 1959 Sep 19;184(Suppl 12):901–902. doi: 10.1038/184901b0. [DOI] [PubMed] [Google Scholar]
  6. Itada N. 18O investigation of pyrocatechase reaction: mode of attack of molecular oxygen. Biochem Biophys Res Commun. 1965 Jul 12;20(2):149–153. doi: 10.1016/0006-291x(65)90338-4. [DOI] [PubMed] [Google Scholar]
  7. Johansson I., Ingelman-Sundberg M. Hydroxyl radical-mediated, cytochrome P-450-dependent metabolic activation of benzene in microsomes and reconstituted enzyme systems from rabbit liver. J Biol Chem. 1983 Jun 25;258(12):7311–7316. [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Latriano L., Zaccaria A., Goldstein B. D., Witz G. Muconaldehyde formation from 14C-benzene in a hydroxyl radical generating system. J Free Radic Biol Med. 1985;1(5-6):363–371. doi: 10.1016/0748-5514(85)90148-5. [DOI] [PubMed] [Google Scholar]
  10. Maltoni C., Conti B., Cotti G. Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology. Am J Ind Med. 1983;4(5):589–630. doi: 10.1002/ajim.4700040503. [DOI] [PubMed] [Google Scholar]
  11. OMURA T., SATO R. THE CARBON MONOXIDE-BINDING PIGMENT OF LIVER MICROSOMES. I. EVIDENCE FOR ITS HEMOPROTEIN NATURE. J Biol Chem. 1964 Jul;239:2370–2378. [PubMed] [Google Scholar]
  12. PARKE D. V., WILLIAMS R. T. Studies in detoxication. XLIX. The metabolism of benzene containing (14C1) benzene. Biochem J. 1953 May;54(2):231–238. doi: 10.1042/bj0540231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Witz G., Rao G. S., Goldstein B. D. Short-term toxicity of trans,trans-muconaldehyde. Toxicol Appl Pharmacol. 1985 Sep 30;80(3):511–516. doi: 10.1016/0041-008x(85)90396-5. [DOI] [PubMed] [Google Scholar]
  14. Yu L. W., Latriano L., Duncan S., Hartwick R. A., Witz G. High-performance liquid chromatography analysis of the thiobarbituric acid adducts of malonaldehyde and trans,trans-muconaldehyde. Anal Biochem. 1986 Aug 1;156(2):326–333. doi: 10.1016/0003-2697(86)90261-7. [DOI] [PubMed] [Google Scholar]

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