Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1972 Jun;128(2):265–277. doi: 10.1042/bj1280265

Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation and metabolism of epoxides related to benzo[a]pyrene and to 7,8- and 9,10-dihydrobenzo[a]pyrene

J F Waterfall 1, P Sims 1
PMCID: PMC1173762  PMID: 5084790

Abstract

Products that appeared to be mainly benzo[a]pyrene 7,8-oxide and benzo[a]pyrene 9,10-oxide were synthesized and their chemical and biochemical properties were investigated. The oxides were unstable and readily rearranged to phenols. They were converted by rat liver homogenates and microsomal preparations into phenols and dihydrodiols, but glutathione conjugates were not formed in appreciable amounts. The dihydrodiols formed from benzo[a]pyrene 7,8- and 9,10-oxide by rat liver microsomal preparations were identical in their chromatographic and spectrographic properties with dihydrodiols formed when benzo[a]pyrene was metabolized by rat liver homogenates. 9,10-Dihydrobenzo[a]pyrene 7,8-oxide and 7,8-dihydrobenzo[a]pyrene 9,10-oxide were also synthesized. They were converted by rat liver homogenates and microsomal preparations into the related cis- and trans-dihydroxy compounds. Glutathione conjugates were formed from the oxides by rat liver homogenates. Both 7,8- and 9,10-dihydrobenzo[a]pyrene were metabolized by rat liver homogenates to mainly the trans-isomers of the related dihydroxy compounds. In experiments with boiled homogenates, the benzo[a]pyrene oxides were converted into phenols, whereas the dihydrobenzo[a]pyrene oxides yielded small amounts of the related dihydroxy compounds.

Full text

PDF
265

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BOYLAND E., SIMS P. METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 9,10-EPOXY-9,10-DIHYDROPHENANTHRENE IN RATS. Biochem J. 1965 Jun;95:788–792. doi: 10.1042/bj0950788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BROOKS C. J., YOUNG L. Biochemical studies of toxic agents. 9. The metabolic conversion of indene into cis- and trans- indane-1: 2-diol. Biochem J. 1956 Jun;63(2):264–269. doi: 10.1042/bj0630264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Booth J., Boyland E., Sato T., Sims P. Metabolism of polycyclic compounds. 17. The reaction of 1:2-dihydronaphthalene and 1:2-epoxy-1:2:3:4-tetrahydronaphthalene with glutathione catalysed by tissue preparations. Biochem J. 1960 Oct;77(1):182–186. doi: 10.1042/bj0770182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyland E., Sims P. Metabolism of polycyclic compounds. 16. The metabolism of 1:2-dihydronaphthalene and 1:2-epoxy-1:2:3:4-tetrahydronaphthalene. Biochem J. 1960 Oct;77(1):175–181. doi: 10.1042/bj0770175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boyland E., Sims P. The metabolism of benz[a]anthracene and dibenz[a,h]anthracene and their 5,6-epoxy-5,6-dihydro derivatives by rat-liver homogenates. Biochem J. 1965 Oct;97(1):7–16. doi: 10.1042/bj0970007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Brooks G. T., Harrison A., Lewis S. E. Cyclodiene epoxide ring hydration by microsomes from mammalian liver and houseflies. Biochem Pharmacol. 1970 Jan;19(1):255–273. doi: 10.1016/0006-2952(70)90346-1. [DOI] [PubMed] [Google Scholar]
  7. Cookson M. J., Sims P., Grover P. L. Mutagenicity of epoxides of polycyclic hydrocarbons correlates with carcinogenicity of parent hydrocarbons. Nat New Biol. 1971 Dec 8;234(49):186–187. doi: 10.1038/newbio234186a0. [DOI] [PubMed] [Google Scholar]
  8. Grover P. L., Hewer A., Sims P. Epoxides as microsomal metabolites of polycyclic hydrocarbons. FEBS Lett. 1971 Oct 15;18(1):76–80. doi: 10.1016/0014-5793(71)80411-8. [DOI] [PubMed] [Google Scholar]
  9. Grover P. L., Sims P., Huberman E., Marquardt H., Kuroki T., Heidelberger C. In vitro transformation of rodent cells by K-region derivatives of polycyclic hydrocarbons. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1098–1101. doi: 10.1073/pnas.68.6.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grover P. L., Sims P. Interactions of the K-region epoxides of phenanthrene and dibenz (a,h)anthracene with nucleic acids and histone. Biochem Pharmacol. 1970 Jul;19(7):2251–2259. doi: 10.1016/0006-2952(70)90124-3. [DOI] [PubMed] [Google Scholar]
  11. HOPKINS R. P., BROOKS C. J., YOUNG L. Biochemical studies of toxic agents. 13. The metabolism of acenaphthylene. Biochem J. 1962 Mar;82:457–466. doi: 10.1042/bj0820457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Huberman E., Aspiras L., Heidelberger C., Grover P. L., Sims P. Mutagenicity to mammalian cells of epoxides and other derivatives of polycyclic hydrocarbons. Proc Natl Acad Sci U S A. 1971 Dec;68(12):3195–3199. doi: 10.1073/pnas.68.12.3195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jerina D. M., Daly J. W., Witkop B., Zaltzman-Nirenberg P., Udenfriend S. 1,2-naphthalene oxide as an intermediate in the microsomal hydroxylation of naphthalene. Biochemistry. 1970 Jan 6;9(1):147–156. doi: 10.1021/bi00803a019. [DOI] [PubMed] [Google Scholar]
  14. Leibman K. C., Ortiz E. Epoxide intermediates in microsomal oxidation of olefins to glycols. J Pharmacol Exp Ther. 1970 Jun;173(2):242–246. [PubMed] [Google Scholar]
  15. Leibman K. C., Ortiz E. Oxidation of indene in liver microsomes. Mol Pharmacol. 1968 May;4(3):201–207. [PubMed] [Google Scholar]
  16. Lewis D. A. The metabolism of cis- and trans-indane-1,2-diol. Biochem J. 1966 Jun;99(3):694–702. doi: 10.1042/bj0990694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Oesch F., Daly J. Solubilization, purification, and properties of a hepatic epoxide hydrase. Biochim Biophys Acta. 1971 Mar 10;227(3):692–697. doi: 10.1016/0005-2744(71)90018-0. [DOI] [PubMed] [Google Scholar]
  18. Pandov H., Sims P. The conversion of phenanthrene 9,10-oxide and dibenz[a,h]anthracene 5,6-oxide into dihydrodiols by a rat-liver microsomal enzyme. Biochem Pharmacol. 1970 Jan;19(1):299–303. doi: 10.1016/0006-2952(70)90349-7. [DOI] [PubMed] [Google Scholar]
  19. Selkirk J. K., Huberman E., Heidelberger C. An epoxide is an intermediate in the microsomal metabolism of the chemical carcinogen, dibenz(a,h)anthracene. Biochem Biophys Res Commun. 1971 Jun 4;43(5):1010–1016. doi: 10.1016/0006-291x(71)90562-6. [DOI] [PubMed] [Google Scholar]
  20. Sims P. Epoxy derivatives of aromatic polycyclic hydrocarbons. The preparation of benz( )anthracene 8,9-oxide and 10,11-dihydrobenz( )anthracene 8,9-oxide and their metabolism by rat liver preparations. Biochem J. 1971 Nov;125(1):159–168. doi: 10.1042/bj1250159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sims P., Grover P. L. Quantitative aspects of the metabolism of 7, 12-dimethylbenz[a]anthracene by liver homogenates from animals of different age, sex and species. Biochem Pharmacol. 1968 Sep;17(9):1751–1758. doi: 10.1016/0006-2952(68)90090-7. [DOI] [PubMed] [Google Scholar]
  22. Sims P. Qualitative and quantitative studies on the metabolism of a series of aromatic hydrocarbons by rat-liver preparations. Biochem Pharmacol. 1970 Mar;19(3):795–818. doi: 10.1016/0006-2952(70)90243-1. [DOI] [PubMed] [Google Scholar]
  23. Sims P. The metabolism of 3-methylcholanthrene and some related compounds by rat-liver homogenates. Biochem J. 1966 Jan;98(1):215–228. doi: 10.1042/bj0980215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sims P. The metabolism of benzo[a]pyrene by rat-liver homogenates. Biochem Pharmacol. 1967 Apr;16(4):613–618. doi: 10.1016/0006-2952(67)90071-8. [DOI] [PubMed] [Google Scholar]
  25. Sims P. The synthesis of 8- and 9-hydroxybenzo[a]pyrene and the role of the products in benzo[a]pyrene metabolism. J Chem Soc Perkin 1. 1968;1:32–34. doi: 10.1039/j39680000032. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES