Abstract
The well-documented mutagenicities and tumorigenicities of many nitro polycyclic aromatic hydrocarbons (nitro PAHs) in experimental models have raised the issue of the potential hazards of exposure to these compounds to humans. While several nitro PAHs have become objects of study due to their quantitative importance in the environment or their extremely potent mutagenic activities in Salmonella tester strains, 6-nitrochrysene (6-NC) came to be of interest primarily because of its highly potent carcinogenic activity in the preweanling mouse bioassay (1–5). However, when applied to mouse skin prior to repeated doses of the tumor promoter 12-0-tetradecanoylphorbol 13-acetate, 6-NC was found to be a weak initiator and, in contrast to the situation in the preweanling mouse model, was less active than the parent compound, chrysene (6,7). It is thus of considerable interest to determine the reason for the high carcinogenic potency of 6-NC in the preweanling mouse and the meaning of the results of the mouse bioassays in terms of assessing the potential risk of 6-NC and related compounds to humans.
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
W. F. Busby, Jr., R. C. Garner, F. L. Chow, C. N. Martin, E. K. Stevens, P. M. Newberne, and G. N. Wogan, 6-Nitrochrysene is a potent tumorigen in newborn mice. Carcinogenesis 6: 801 (1985).
P. G. Wislocki, E. S. Eagan, A. Y. H. Lu, K. L. Dooley, P. P. Fu, H. Han-Hsu, F. A. Beland, and F. F. Kadlubar, Tumorigenicity of nitrated derivatives of pyrene, benz[a]anthracene, chrysene and benzo[a]pyrene in the newborn mouse assay. Carcinogenesis 7: 1317 (1986).
W. F. Busby, Jr., E. K. Stevens, E. R. Kellenbach, J. Cornelisse, and J. Lugtenburg, Dose-response relationships of the tumorigenicity of cyclopenta[c,d]pyrene, benzo[a]pyrene and 6-nitrochrysene in a newborn mouse lung adenoma bioassay. Carcinogenesis 9: 741 (1988).
K. El-Bayoumy, G.-H. Shiue, and S. S. Hecht, Comparative tumorigenicity of 6-nitrochrysene and its metabolites in newborn mice. Carcinogenesis 10: 369 (1989).
W. F. Busby, Jr., E. K. Stevens, C. N. Martin, F. L. Chow, and R. C. Garner, Comparative tumorigenicity of parent and mononitro-polynuclear aromatic hydrocarbons in the BLU:Ha newborn mouse assay. Toxicol. Appl. Pharm. 99: 555 (1989).
K. El-Bayoumy, S. S. Hecht, and Hoffmann, D., Comparative tumor initiating activity on mouse skin of 6-nitrobenzo[a]pyrene, 6-nitrochrysene, 3-nitroperylene, l-nitropyrene and their parent hydrocarbons. Cancer Lett. 16: 333, (1982).
M. Sala, C. Lasne, Y. P. Lu, and I. Chouroulinkov, Morphological transformation in three mammalian cell systems following treatment with 6-nitrochrysene and 6-nitrobenzo[a]pyrene. Carcinogenesis 8: 503 (1987).
G. Rudali, N. P. Buu-Hoi, and A. Lacassagne, Sur quelques effets biologiques du 2-amino-chrysene. C. R. Acad. Sci. (Paris) 236: 2020 (1953).
G. Lambelin, G. Mees, and N. P. Buu-Hoi, Chronic toxicity studies of 6-aminochrysene in the rat. Arzneim.-Forsch. 17: 1117 (1967).
F. J. C. Roe, R. L. Carter, and S. Adamthwaite, Induction of liver and lung tumours in mice by 6-aminochrysene administered during the first three days of life. Nature 221: 1063 (1969).
G. Lambelin, J. Roba, R. Roncucci, and R. Parmentier, Carcinogenicity of 6-aminochrysene in mice. Eur. J. Cancer 11: 327 (1975).
K. El-Bayoumy and S. S. Hecht, Identification of trans-1,2-dihydro1,2-dihydroxy-6-nitrochrysene as a major mutagenic metabolite of 6-nitrochrysene. Cancer Res. 44: 3408 (1984).
K. El-Bayoumy, K. B. Delclos, R. H. Heflich, R. Walker, G.-H. Shiue, and S. S. Hecht, Mutagenicity, metabolism and DNA adduct formation of 6-nitrochrysene in Salmonella typhimurium. Mutagenesis 4: 235 (1989)
J. Gelzer and P. Loustalot, Chrysenex in experimental advanced mammary cancer. Eur. J. Cancer 3: 79 (1967).
H. J. Tagnon, A. Coure, S. Garattini, R. Rosso, G. Lambelin, M. Gautier, and N.P. Buu-Hoi, The antitumoral activity of some derivatives of 6-aminochrysene. Fur. J. Cancer 6: 81 (1970).
N. P. Buu-Hoi, D.-P. Hien, and P. Mabille, Some biological properties of 6-aminochrysene and its derivatives, a family of carcinostatic compounds devoid of cytotoxic action, in: “Cancer Chemotherapy. Proc. Takeda Int. Conf., Osaka”, A. Goldin, ed., Maruzen Co., Tokyo (1966).
Groupe, Europeen du Cancer du Sein, Induction par le 6-aminochrysene de remission du cancer du sein en phase avancee chez la femme. Eur. J. Cancer 3: 75 (1967).
K. B. Delclos, D. W. Miller, J. O. Lay, Jr., D. A. Casciano, R. P. Walker, P. P. Fu, and F. F. Kadlubar, Identification of C8-modified deoxyinosine and N2- and C8-modified deoxyguanosine as major products of the in vitro reaction of N-hydroxy-6-aminochrysene with DNA and the formation of these adducts in isolated rat hepatocytes treated with 6-nitrochrysene and 6-aminochrysene. Carcinogenesis 8: 1703 (1987).
K. B. Delclos, R. P. Walker, K. L. Dooley, P. P. Fu, and F. F. Kadlubar, Carcinogen-DNA adduct formation in the lungs and livers of preweanling CD-1 male mice following ldministration of [3H]-6-nitrochrysene, [3H]-6-aminochrysene, and [3H]-1,6-dinitropyrene. Cancer Res. 47: 6272 (1987).
K. B. Delclos, K. El-Bayoumy, S. S. Hecht R. P. Walker, and F. F. Kadlubar, Metabolism of the carcinogen [3H]6-nitrochrysene in the preweanling mouse: identification of 6-aminochrysene-1,2-dihydrodiol as the probable proximate carcinogenic metabolite. Carcinogenesis 9: 1875 (1988).
I. R. Rowland, Interactions of the gut microflora and the host in toxicology. Tox. Path. 16: 147 (1988). _
K. B. Delclos, K. El-Bayoumy, D. A. Casciano, R. P. Walker, F. F. Kadlubar, S. S. Hecht, N. Shivapurkar, S. Mandal, and G. D. Stoner, Metabolic activation of 6-nitrochrysene in explantsof human bronchus an in isolated rat hepatocytes. Cancer Res. 49: 2909 (1989).
R. C. Gupta, Non-random binding of the carcinogen N-hydroxy-2-AAF to repetitive sequences of rat liver DNA in vivo. Proc. Natl. Acad. Sci. (USA) 81: 6943 (1984).
M. V. Reddy and K. Randerath, Nuclease P1-mediated enhancement of sensitivity of 32P-postlabeling test for structurally diverse DNA adducts. Carcinogenesis 7: 1543 (1986).
J. P. Sculier, C. Brassinne, C. Laduron, A. Coune, C. Ho]laert, and C. Delcroix, A phase I study, with pharmacokinetic analysis, of intravenous administration of 6-aminochrysene entrapped into sonicated liposomes in patients with advanced cancer. J. Liposome Res., in press
M. Jeanpierre, A rapid method for the purification of DNA from blood. Nucleic Acids Res. 15: 9611 (1987).
J. Schilhabel and K. Levsen, Identification of nitrated polycyclic hydrocarbons in diesel particulate extracts by negative ion chemical ionization and tandem mass spectrometry. Fresenius Z. Anal. Chem. 333: 800 (1989).
R. C. Garner, C. A. Stanton, C. N. Martin, F. L. Chow, W. Thomas, D. Hubner, and R. Herrmann, Bacterial mutagenicity and chemical analysis of polycyclic aromatic hydrocarbons and some nitro derivatives in environmental samples collected in West Germany. Environ. Mut. 8: 109 (1986).
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
Delclos, K.B., Talaska, G., Walker, R.P., Brassinne, C., Sculier, J.P. (1990). Metabolic Activation of 6-Nitrochrysene and 6-Aminochrysene in Vitro and in Vivo . 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_27
Download citation
DOI: https://doi.org/10.1007/978-1-4615-3800-4_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6694-2
Online ISBN: 978-1-4615-3800-4
eBook Packages: Springer Book Archive