Abstract
A number of nitropolycyclic aromatic hydrocarbons (NO2-PAH) have been identified in environmental sources(1–3). 1-Nitropyrene (1-NP), a representative example, is a bacterial mutagen and an animal tumorigen and has been reported to be the most abundant NO2-PAH in sources such as diesel engine emission (4). 1-NP is activated in bacterial systems (5,6) via nitro-reduction to yield a major DNA adduct, N-(deoxyguanosin-8-y1)l-aminopyrene (N-dG-1-AP). However, studies carried out in our laboratory as well as in others indicate that simple nitro-reduction of 1-NP cannot account for the observed DNA adducts in vivo and in vitro (7–12). In order to more clearly define the metabolic activation of 1-NP, additional DNA adduct markers are required. Therefore, in this paper we present our initial results on the identification of a major adduct formed from the incubation of DNA with 4, 5-epoxy-4, 5-dihydro-l-nitropyrene (1-NP-4, 5-oxide), a mutagenic ring oxidized metabolite of 1-NP. We have also established the 32P- fingerprints of the DNA adducts derived from 1-NP-4, 5-oxide.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Rosenkranz, H.S., and Mermelstein, R. The genotoxicity, metabolism and carcinogenicity of nitrated polycyclic aromatic hydrocarbons. J. Environ. Sci. Health, C3: 221–272, 1985.
Tokiwa, H., and Ohnishi, Y. Mutagenicity and carcinogenicity of nitroarenes and their sources in the environment. Crit. Rev. Toxicol., 17: 23–60, 1986.
Fu, P. P., Chou, M. W., and Beland, F.A. Effects of nitro substitution on the in vitro metabolic activation of polycyclic aromatic hydrocarbons. In: S. D. Yang and B. D. Silverman (eds.), Polycyclic Aromatic Hydrocarbon Carcinogenesis: structure Activity Relationships, Vol. 2, pp. 37–65. Boca Raton: CRC Press, Inc., 1988.
Schuetzle, D. Sampling of vehicle emissions for chemical analysis and biological testing. Environ. Health Perspect., 47: 65–80, 1983.
Howard, P. C., Heflich, R. H., Evans, F. E., and Beland, F. A. Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene. Cancer Res., 43: 2052–2058, 1983.
Messier, F., Lu, C., Andrews, P., McCarry, B. E., Quilliam, M. A., and McCalla, D. R. Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium. Carcinogenesis, 2: 1007–1011, 1981.
Djuric, Z., Fifer, D. R., Howard, P.C., and Beland, F.A. Oxidative microsomal metabolism of 1-nitropyrene and DNA-binding of oxidized metabolites following nitroreduction. Carcinogenesis, 7: 1073–1079, 1986.
Jackson, M. A., King, L. C., Ball, L. M., Ghayourmanesh, S., Jeffrey, A. M., and Lewtas, J. Nitropyrene: DNA binding and adduct formation in respiratory tissues. Environ. Health Perspect., 62: 203–207, 1985.
Mitchell, C. E. Formation of DNA adducts in mouse tissues after intratracheal instillation of 1-nitropyrene. Carcinogenesis, 9: 857–860, 1988.
El-Bayoumy, K. E., Shiue, G.-H., and Hecht, S. S. Metabolism and DNA binding of 1-nitropyrene and 1-nitrosopyrene in newborn mice. Chem. Res. Tox., 1: 243–247, 1988.
Stanton, C. A., Chow, F. L., Phillips, D. H., Grover, P. L., Garner, R. C., and Martin, C. N. Evidence for N-(deoxyguanosin-8-y1)-l-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene. Carcinogenesis, 6: 535–538,1985.
Roy, A. K., El-Bayoumy, К., and Hecht, S. S. 32P-postlabeling analysis of 1-nitropyrene-DNA adducts in female Sprague-Dawley rats. Carcinogenesis, 10: 195–198, 1989.
El-Bayoumy, K., Rivenson, A., Johnson, B., DiBello, J., Little, P., and Hecht, S. S. Comparative tumorigenicity of 1-nitropyrene, 1-nitrosopyrene, and 1-aminopyrene administered by gavage to Sprague-Dawley rats. Cancer Res., 48, 4526–4260, 1988.
Fifer, E.K., Howard, P.C., Heflich, R.H. and Beland, F.A. Synthesis and mutagenicity of 1-nitropyrene-4,5-oxide and 1-nitropyrene-9,10-oxide, microsomal metabolites of 1-nitropyrene. Mutagenesis, 1: 433–438, 1986.
El-Bayoumy, K., Villucci, P., Roy, A. K., and Hecht, S. S. Synthesis of K-region derivatives of the carcinogen 1-nitropyrene. Carcinogenesis, 7: 1577–1580, 1986.
Martin, C. N., Beland, F. A., Roth, R. W., Kadlubar, F. F. Covalent binding of benzidine and N-acetylbenzidine to DNA at the C-8 atom of deoxyguanosine in vivo and in vitro. Cancer Res., 42: 2678–2696, 1982.
Gupta, R. C., Reddy, М. V., and Randerath, K. 32P-postlabelling analysis of non-radioactive aromatic carcinogen-DNA adducts. Carcinogenesis, 3: 1081–1092, 1982.
Gupta, R. C. Enhanced sensitivity of 32P-postlabelling analysis of aromatic carcinogen: DNA adducts. Cancer Res., 45: 5656–5662, 1985.
Loveless, A. Possible relevance of 0–6 alkylation of deoxyguanosine to the mutagenicity and carcinogenicity of nitrosamines and nitrosamides. Nature, 223: 206–207, 1969.
Moore, P. D., and Koreeda, M. Application of the change in partition coefficient with pH to the structure determination of alkyl substituted guanosines. Biochem. Biophys. Res. Commun., 73: 459–464, 1976.
Preuss-Schwartz, D., and Baird, W. M. Benzo[a]pyrene: DNA adduct formation in early-passage wistar rat embryo cell culture: evidence for multiple pathways of activation of benzo[a]pyrene. Cancer Res., 46: 545–552, 1986.
Jeffrey, A. M., Blobstein, S. H., Weinstein, I. B., Beland, F. A., Harvey, R. G., Kasai, H., and Nakanishi, K. Structure of 7, 12-dimethylbenz[а]anthraceneguanosine adducts. Proc. Natl. Acad. Sci., 73: 2311–2315, 1976.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1990 Springer Science+Business Media New York
About this chapter
Cite this chapter
El-Bayoumy, K., Roy, A.K., Hecht, S.S. (1990). Products Obtained by in Vitro Reaction of 4, 5-Epoxy-4, 5-Dihydro-1-Nitropyrene with DNA. In: Howard, P.C., Hecht, S.S., Beland, F.A. (eds) Nitroarenes. Environmental Science Research, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3800-4_25
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3800-4_25
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6694-2
Online ISBN: 978-1-4615-3800-4
eBook Packages: Springer Book Archive