Skip to main content
NCBI home page
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
. 1980 Aug;77(8):4554–4558. doi: 10.1073/pnas.77.8.4554

Fungal oxidation of (+/-)-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene: formation of diastereomeric benzo[a]pyrene 9,10-diol 7,8-epoxides.

C E Cerniglia, D T Gibson
PMCID: PMC349882  PMID: 6933504

Abstract

The filamentous fungus Cunninghamella elegans oxidized (+/-) trans-9,10-dihydroxy-9,10-dihydrobenzo[a]-pyrene to a complex mixture of metabolites which were detected by high-pressure liquid chromatography. Two of the metabolites were identified as (+/-)7 beta, 8 alpha, 9 alpha, 10 beta-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene and (+/-)-7 beta,8 alpha,9 beta,10 alpha-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene. A third product gave absorption and mass spectra consistent with a diol-epoxide structure. Hydrolysis of this compound gave (+/-)-7 beta, 8 alpha, 9 beta, 10 alpha-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene as the major identifiable product with a minor unidentified tetraol. Synthetic (+/-)-9 alpha, 10 beta-dihydroxy-7 beta, 8 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene gave the same hydrolysis products and had the same retention time on high-pressure liquid chromatography as did the fungal metabolite. The trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene recovered at the end of the experiment showed no optical activity, indicating that both enantiomers were metabolized by the fungus. the results suggest that C. elegans oxidizes (+/-)-trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene to diastereomeric benzo[a]pyrene 9,10-diol 7,8-epoxides.

Full text

PDF
4554

Selected References

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

  1. Booth J., Sims P. Different pathways involved in the metabolism of the 7,8- and 9,10-dohydrodiols of benzo(a)pyrene. Biochem Pharmacol. 1976 Apr 15;25(8):979–980. doi: 10.1016/0006-2952(76)90326-9. [DOI] [PubMed] [Google Scholar]
  2. Buening M. K., Wislocki P. G., Levin W., Yagi H., Thakker D. R., Akagi H., Koreeda M., Jerina D. M., Conney A. H. Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5358–5361. doi: 10.1073/pnas.75.11.5358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cerniglia C. E., Gibson D. T. Fungal oxidation of benzo[a]pyrene and (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene. Evidence for the formation of a benzo[a]pyrene 7,8-diol-9,10-epoxide. J Biol Chem. 1980 Jun 10;255(11):5159–5163. [PubMed] [Google Scholar]
  4. Cerniglia C. E., Gibson D. T. Oxidation of benzo[a]pyrene by the filamentous fungus Cunninghamella elegans. J Biol Chem. 1979 Dec 10;254(23):12174–12180. [PubMed] [Google Scholar]
  5. Cerniglia C. E., Perry J. J. Crude oil degradation by microorganisms isolated from the marine environment. Z Allg Mikrobiol. 1973;13(4):299–306. doi: 10.1002/jobm.3630130403. [DOI] [PubMed] [Google Scholar]
  6. Cohen G. M., Moore B. P. The metabolism of benzo(a)pyrene, 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and 9,10-dihydro-9,10-dihydroxybenzono leads to (a)pyrene by short-term organ cultures of hamster lung. Biochem Pharmacol. 1977 Aug 15;26(16):1481–1487. doi: 10.1016/0006-2952(77)90419-1. [DOI] [PubMed] [Google Scholar]
  7. Ferris J. P., MacDonald L. H., Patrie M. A., Martin M. A. Aryl hydrocarbon hydroxylase activity in the fungus Cunninghamella bainieri: evidence for the presence of cytochrome P-450. Arch Biochem Biophys. 1976 Aug;175(2):443–452. doi: 10.1016/0003-9861(76)90532-4. [DOI] [PubMed] [Google Scholar]
  8. Gibson D. T., Mahadevan V., Jerina D. M., Yogi H., Yeh H. J. Oxidation of the carcinogens benzo [a] pyrene and benzo [a] anthracene to dihydrodiols by a bacterium. Science. 1975 Jul 25;189(4199):295–297. doi: 10.1126/science.1145203. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Slaga T. J., Bracken W. M., Viaje A., Levin W., Yagi H., Jerina D. M., Conney A. H. Comparison of the tumor-initiating activities of benzo(a)pyrene arene oxides and diol-epoxides. Cancer Res. 1977 Nov;37(11):4130–4133. [PubMed] [Google Scholar]
  12. Thakker D. R., Yagi H., Akagi H., Koreeda M., Lu A. H., Levin W., Wood A. W., Conney A. H., Jerina D. M. Metabolism of benzo[a]pyrene. VI. Stereoselective metabolism of benzo[a]pyrene and benzo[a]pyrene 7,8-dihydrodiol to diol epoxides. Chem Biol Interact. 1977 Mar;16(3):281–300. doi: 10.1016/0009-2797(77)90108-9. [DOI] [PubMed] [Google Scholar]
  13. Thakker D. R., Yagi H., Lehr R. E., Levin W., Buening M., Lu A. Y., Chang R. L., Wood A. W., Conney A. H., Jerina D. M. Metabolism of trans-9,10-dihydroxy-9,10-dihydrobenzo[a]pyrene occurs primarily by arylhydroxylation rather than formation of a diol epoxide. Mol Pharmacol. 1978 May;14(3):502–513. [PubMed] [Google Scholar]
  14. Thakker D. R., Yagi H., Lu A. Y., Levin W., Conney A. H. Metabolism of benzo[a]pyrene: conversion of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene to highly mutagenic 7,8-diol-9,10-epoxides. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3381–3385. doi: 10.1073/pnas.73.10.3381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Wood A. W., Chang R. L., Levin W., Yagi H., Thakker D. R., Jerina D. M., Conney A. H. Differences in mutagenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides. Biochem Biophys Res Commun. 1977 Aug 22;77(4):1389–1396. doi: 10.1016/s0006-291x(77)80133-2. [DOI] [PubMed] [Google Scholar]
  16. Yang S. K., McCourt D. W., Gelboin H. V., Miller J. R., Roller P. P. Stereochemistry of the hydrolysis products and their acetonides of two stereoisomeric benzo[a]pyrene 7,8-diol 9,10-epoxides. J Am Chem Soc. 1977 Jul 20;99(15):5124–5130. doi: 10.1021/ja00457a036. [DOI] [PubMed] [Google Scholar]
  17. Yang S. K., McCourt D. W., Roller P. P., Gelboin H. V. Enzymatic conversion of benzo(a)pyrene leading predominantly to the diol-epoxide r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene through a single enantiomer of r-7, t-8-dihydroxy-7,8-dihydrobenzo(a)pyrene. Proc Natl Acad Sci U S A. 1976 Aug;73(8):2594–2598. doi: 10.1073/pnas.73.8.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES