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
. 1978 Apr;75(4):1667–1669. doi: 10.1073/pnas.75.4.1667

Cyclopenta[c,d]pyrene: a highly mutagenic polycyclic aromatic hydrocarbon.

E Eisenstadt, A Gold
PMCID: PMC392399  PMID: 347443

Abstract

A polycyclic aromatic hydrocarbon recently isolated from carbon black and identified as cyclopenta[c,d]pyrene (CPP) is highly mutagenic. By the criteria of the Salmonella/mammalian-microsome mutagenicity test, the mutagenic potency of CPP is equalled by only two other naturally occurring polycyclic aromatic hydrocarbons--benzo[a]pyrene and dibenz[a,c]anthracene. The potent mutagenicity of CPP is noteworthy for two reasons: (i) CPP is a mutagenic polycyclic aromatic hydrocarbon without a "bay-region" and (ii) there is evidence that it is distributed widely in the environment. On the basis of experimental observations and perturbational molecular orbital calculations we propose that a mutagenic metabolite of CPP will be the 3,4-oxide. The carbonium ion derived from opening of CPP 3,4-oxide is identical to that derived from opening of benzo[a]pyrene 7,8-diol-9,10-oxide, the metabolite now thought to be an ultimate mutagenic and carcinogenic species.

Full text

PDF
1667

Selected References

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

  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Borgen A., Darvey H., Castagnoli N., Crocker T. T., Rasmussen R. E., Wang I. Y. Metabolic conversion of benzo(a)pyrene by Syrian hamster liver microsomes and binding of metabolites to deoxyribonucleic acid. J Med Chem. 1973 May;16(5):502–506. doi: 10.1021/jm00263a020. [DOI] [PubMed] [Google Scholar]
  3. Daudel P., Duquesne M., Vigny P., Grover P. L., Sims P. Fluorescence spectral evidence that benzo(a)pyrene-DNA products in mouse skin arise from diol-epoxides. FEBS Lett. 1975 Oct 1;57(3):250–253. doi: 10.1016/0014-5793(75)80310-3. [DOI] [PubMed] [Google Scholar]
  4. Gamper H. B., Tung A. S., Straub K., Bartholomew J. C., Calvin M. DNA strand scission by benzo[a]pyrene diol epoxides. Science. 1977 Aug 12;197(4304):671–674. doi: 10.1126/science.877583. [DOI] [PubMed] [Google Scholar]
  5. Gold A. Carbon black absorbates: separation and identification of a carcinogen and some oxygenated polyaromatics. Anal Chem. 1975 Jul;47(8):1469–1472. doi: 10.1021/ac60358a002. [DOI] [PubMed] [Google Scholar]
  6. Lee M. L., Prado G. P., Howard J. B., Hites R. A. Source identification of urban airborne polycyclic aromatic hydrocarbons by gas chromatographic mass spectrometry and high resolution mass spectrometry. Biomed Mass Spectrom. 1977 Jun;4(3):182–185. doi: 10.1002/bms.1200040311. [DOI] [PubMed] [Google Scholar]
  7. McCann J., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci U S A. 1976 Mar;73(3):950–954. doi: 10.1073/pnas.73.3.950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. McCann J., Spingarn N. E., Kobori J., Ames B. N. Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A. 1975 Mar;72(3):979–983. doi: 10.1073/pnas.72.3.979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Neal J., Trieff N. M. Isolation of an unknown carcinogenic polycyclic hydrocarbon from carbon blacks. Health Lab Sci. 1972 Jan;9(1):32–38. [PubMed] [Google Scholar]
  11. Sims P., Grover P. L. Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis. Adv Cancer Res. 1974;20:165–274. doi: 10.1016/s0065-230x(08)60111-6. [DOI] [PubMed] [Google Scholar]
  12. Sims P., Grover P. L., Swaisland A., Pal K., Hewer A. Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide. Nature. 1974 Nov 22;252(5481):326–328. doi: 10.1038/252326a0. [DOI] [PubMed] [Google Scholar]
  13. Weinstein I. B., Jeffrey A. M., Jennette K. W., Blobstein S. H., Harvey R. G., Harris C., Autrup H., Kasai H., Nakanishi K. Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo. Science. 1976 Aug 13;193(4253):592–595. doi: 10.1126/science.959820. [DOI] [PubMed] [Google Scholar]
  14. Wood A. W., Chang R. L., Levin W., Lehr R. E., Schaefer-Ridder M., Karle J. M., Jerina D. M., Conney A. H. Mutagenicity and cytotoxicity of benz[alpha]anthracene diol epoxides and tetrahydro-epoxides: exceptional activity of the bay region 1,2-epoxides. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2746–2750. doi: 10.1073/pnas.74.7.2746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Yang S. K., McCourt D. W., Gelboin H. V. The mechanism of hydrolysis of the non-K-region benzo[a]pyrene diol epoxide r-7, t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene. J Am Chem Soc. 1977 Jul 20;99(15):5130–5134. doi: 10.1021/ja00457a037. [DOI] [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