Advertisement

Morphological Cell Transformation and DNA Adduction by Benz(J)Aceanthrylene and its Presumptive Reactive Metabolites in C3H10T1/2CL8 Cells

  • Jessica Lasley
  • Susan Curti
  • Jeffrey Ross
  • Garret Nelson
  • Ramiah Sangaiah
  • Avram Gold
  • Stephen Nesnow
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)

Abstract

Benz(j)aceanthrylene [B(j)A], a cyclopenta-fused polycyclic aromatic hydrocarbon found in coal combustion emissions [Grimmer et al., 1985; Schmidt et al., 1986], is a strong inducer of morphological transforming activity in C3H10T1/2CL8 (C3H10T1/2) mouse embryo fibroblasts [Mohapatra et al., 1987]. The metabolism of B(j)A by these cells has been studied and the results differ from those found with Aroclor-1254 induced rat liver S9. In C3H10T1/2 cells the major metabolite is 9,10dihydro-9,10-dihydroxy-B(j)A with minor amounts of 1,2-dihydro-1,2-dihydroxy-B(j)A [Mohapatra et al., 1987], while in rat liver S9 the major metabolite is 1,2-dihydro-1,2-dihydroxy-B(j)A [Nesnow et al., 1988]. These results suggest that while the major route of metabolic activation by Aroclor-1254 induced rat liver S9 is through B(j)A-1,2-oxide, the arene oxide at the cyclopenta-ring, metabolic activation of B(j)A in C3H10T1/2 cells might be via two routes: botharene oxide [B(j)A-1,2-oxide] formation and bay-region diol-epoxide formation [9,10-dihydro-9,10-dihydroxy-B(j)A-7,8-oxide]. This study was undertaken to clarify the role of the putative reactive intermediates, 9,10-dihydro-9,10-dihydroxy-B(j)A-7,8-oxide [B(j)A-diol-epoxide], and B(j)A-1,2-oxide in the metabolic activation of B(j)A in C3H10T1/2 cells.

Keywords

Polycyclic Aromatic Hydrocarbon Mouse Embryo Fibroblast Grand Island Biological Arene Oxide Mouse Embryo Fibroblast Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

B(j)A

benz(j)aceanthrylene

C3H10T1/2

C3H10T1/2CL8

B(j)A-diolepoxide

9,10-dihydro-9,10-dihydroxy-B(j)A-7,8-oxide

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bartczak, A.W., Sangaiah, R., Ball, L.M., Warren, S.H. and Gold, A. (1987). Synthesis and bacterial mutagenicity of the cyclopenta oxides of the four cyclopenta-fused isomers of benzanthracene. Mutagenesis 2, 101–105.CrossRefPubMedGoogle Scholar
  2. Grimmer, G., Jacob, J., Dettbarn, G. and Naujack, K.W. (1985). Determination of polycyclic aromatic hydrocarbons, azaarenes, and thiaarenes emitted from coal-fired residential furnaces by gas chromatographic/mass spectrometry. Fresenius Z. Anal. Chem. 322, 595–602.CrossRefGoogle Scholar
  3. Gupta, RC. (1985). Enhanced sensitivity of 32P-postlabeling analysis of aromatic carcinogen:DNA adducts. Cancer Res. 45, 5656–5662.PubMedGoogle Scholar
  4. Mohapatra, N., MacNair, P., Bryant, B.J., Ellis, S., Rudo, K., Sangaiah, R., Gold, A. and Nesnow, S. (1987). Morphological transforming activity and metabolism of cyclopenta-fused isomers of benz[alanthracene in mammalian cells. Mutation Res. 188, 323–334.CrossRefPubMedGoogle Scholar
  5. Nesnow, S., Garland, H. and Curtis, G. (1982). Improved transformation of C3H10T1/2CL8 cells by direct-and indirect-acting carcinogens. Carcinogenesis 3, 377–380.CrossRefPubMedGoogle Scholar
  6. Nesnow, S., Easterling, R.E., Ellis, S., Watts, R. and Ross, J. (1988). Metabolism of benz(j)aceanthrylene (cholanthrylene) and benz(1)aceanthrylene by induced rat liver S9. Cancer Lett. 39, 19–27.CrossRefPubMedGoogle Scholar
  7. Nesnow, S., Ross, J., Mohapatra, N., Gold, A., Sangaiah, R. and Gupta, R. (1989). DNA adduct formation, metabolism, and morphological transforming activity of aceanthrylene in C3H10T1/2CL8 cells. Mutation Res. 222, 223–235.CrossRefPubMedGoogle Scholar
  8. Reddy, M.V. and Randerath, K. (1986). Nuclease Pl-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis 7, 1542–1551.CrossRefGoogle Scholar
  9. Reznikoff, C.A., Bertram, J.S., Brankow, D.W. and Heidelberger, C. (1973). Quantitative and qualitative studies of chemical transformation of cloned C3H mouse embryo cells sensitive to post confluence inhibition of cell division. Cancer Res. 33, 3239–3249.Google Scholar
  10. Ross, J., Nelson, G., Kligerman, A., Erexson, G., Bryant, M., Earley, K., Gupta, R. and Nesnow, S. Formation and persistence of novel benzo(a)pyrene adducts in rat lung, liver and peripheral blood lymphocyte DNA. Submitted.Google Scholar
  11. Schmidt, W., Grimmer, G., Jacob, J. and Dettbarn, G. (1986). Polycyclic aromatic hydrocarbons and thiaarenes in the emission from hard coal combustion. Toxicol. Environ. Chem. 13, 1–16.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Jessica Lasley
    • 1
  • Susan Curti
    • 1
  • Jeffrey Ross
    • 2
  • Garret Nelson
    • 1
  • Ramiah Sangaiah
    • 3
  • Avram Gold
    • 3
  • Stephen Nesnow
    • 2
  1. 1.Environmental Health ResearchU.S. Environmental Protection AgencyResearch Triangle ParkUSA
  2. 2.Testing and Carcinogenesis and Metabolism BranchU.S. Environmental Protection AgencyResearch Triangle ParkUSA
  3. 3.Department of Environmental Sciences and EngineeringUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations