Carbocations from oxidized metabolites of benzo[a]anthracene: A computational study of their methylated and fluorinated derivatives and guanine adducts

Chemical Research in Toxicology

Volumn 19, Issue 7, 2006, Pages 899-907

  Borosky, Gabriela L ^a   Laali, Kenneth K ^b  

^a UNIVERSIDAD NACIONAL DE CÓRDOBA   (Argentina)

^b KENT STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZ[A]ANTHRACENE; BENZ[A]ANTHRACENE DERIVATIVE; CARBOCATION; CATION; EPOXIDE; FLUORINE DERIVATIVE; GUANINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CALCULATION; COVALENT BOND; DENSITY FUNCTIONAL THEORY; ENERGY TRANSFER; FLUORINATION; GEOMETRY; METABOLITE; METHYLATION; MOLECULAR STABILITY; OXIDATION; PHASE TRANSITION; PROTON TRANSPORT; STRUCTURE ACTIVITY RELATION;

BENZ(A)ANTHRACENES; BIOTRANSFORMATION; CATIONS; COMPUTER SIMULATION; DNA ADDUCTS; FLUORINE; GUANINE; METHYLATION; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; OXIDATION-REDUCTION; SIGNAL TRANSDUCTION;

EID: 33746211296     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx060067l     Document Type: Article

References (72)

1. International Agency for Research on Cancer (1983) IARC Monographs on the Evaluation of Carcinogenic Risks of Chemicals to Humans. Vol. 32: Polycyclic Aromatic Compounds, Part 1, Chemical, Environmental and Experimental Data, IARC, Lyon, France.
2. Harvey, R. G. (1991) Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogenicity, Cambridge University Press, Cambridge, U.K.
3. Fetzer, S. M., Huang, C.-R., Harvey, R. G., and LeBreton, P. R. (1993) Photoelectron and ab initio molecular orbital investigations of genotoxic benz[a]anthracene metabolites: electronic influences on DNA binding. J. Phys. Chem. 97, 2385-2394 and references therein.
4. Hecht, S. S., Melikian, A. A., and Amin, S. (1988) Effect of methyl substitution on the tumorigenicity and metabolic activation of polycyclic aromatic hydrocarbons. In Polycyclic Aromatic Hydrocarbon Carcinogenesis: Structure-Activity Relationships (Yang, S. K., and Silverman B. D., Eds.) Vol 1, pp 95-128. CRS Press, Boca Raton, FL.
5. Wood, A. W., Levin, W., Chang, R. L., Lehr, R. E., Schaefer-Ridder, M., Karle, J. M., Jerina, D. M., and Conney, A. H. (1977) Tumorigenicity of five dihydrodiols of benz[a]anthracene on mouse skin: exceptional activity of benz[a]anthracene-3,4-diol. Proc. Natl. Acad. Sci. U.S.A. 74, 3176-3179.
6. Wislocki, P. G., Fiorentini, K. M., Fu, P. P., Yang, S. K., and Lu, A. Y. (1982) Tumor-initiating ability of the twelve monomethylbenz[a]-anthracenes. Carcinogenesis 3, 215-217.
7. Pataki, J., and Huggins, C. (1969) Molecular site of substituents of benz[a]anthracene related to carcinogenicity. Cancer Res. 29, 506-509.
8. Sugiyama, T. (1973) Chromosomal aberrations and carcinogenesis by various benz[a]anthracene derivatives. Gann 64, 637-639.
9. Muggins, C. B., Pataki, J., and Harvey, R. G. (1967) Geometry of carcinogenic polycyclic aromatic hydrocarbons. Proc. Natl. Acad. Sci. U.S.A. 58, 2253-2260.
10. Dipple, A., Moschel, R. C., and Bigger, C. A. H. (1984) Polynuclear aromatic carcinogens. In Chemical Carcinogens (Searle, C. E., Ed.) Vol. 1, pp41 -163, ACS Monograph 182, American Chemical Society, Washington, DC.
11. Xue, W., and Warshawsky, D. (2005) Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review. Toxicol. Appl. Pharmacol. 206, 73-93.
12. Kumar, M. N. V. R., Vadhanam, M. V., Horn, J., Flesher, J. W., and Gupta, R. C. (2005) Formation of benzylic-DNA adducts resulting from 7,12-dimethylbenz[a]anthracene in vivo. Chem. Res. Toxicol. 18, 686-691.
13. Hecht, S. S., Amin, S., Melikian, A. A., La Voie, E. J., and Hoffman, D. (1985) Effect of methyl and fluorine substitution on the metabolic activation and tumorigenicity of polycyclic aromatic hydrocarbons. In Polycyclic Hydrocarbons and Carcinogenesis (Harvey, R. G., Ed.) ACS Symposium Series 283, Chapter 2, pp 85-105, American Chemical Society, Washington, DC.
14. DiGiovanni, J., Decina, P. C., and Diamond, L. (1983) Tumor-initiating activity of 9- and 10-fluoro-7.12-dimethylbenz[a]anthracene (DMBA) and the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on tumor-initiation by monofluoro derivatives of DMBA in SENCAR mice. Carcinogenesis 4, 1045-1049.
15. Diamond, L., Cherian, K., Harvey, R. G., and DiGiovanni, J. (1984) Mutagenic activity of methyl- and fluoro-substituted derivatives of polycyclic aromatic hydrocarbons in a human hepatoma (HepG2) cell-mediated assay. Mutat. Res. 136, 65-72.
16. Sawyer, T. W., Fisher, E. P., and DiGiovanni, J. (1987) Skin tumor-initiating activities of 9- and 10-fluoro derivatives of 7- or 12-methylbenz[a]anthracene in SENCAR mice. Carcinogenesis 8, 1465-1468.
17. Harvey, R. G., and Dunne, F. B. (1978) Multiple regions of metabolic activation of carcinogenic hydrocarbons. Nature 273, 566-568.
18. DiGiovanni, J., Diamond, L., Singer, J. M., Daniel, F. B., Witiak, D. T., and Slaga, T. J. (1982) Tumor-initiating activity of 4-fluoro-7,-12- dimethylbenz[a]anthracene and 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene in female SENCAR mice. Carcinogenesis 3, 651-655.
19. Black, S. D., Sharma, P. K., Gallucci, J. C., Blackburn, A. C., Downs, J. W., Rinderle, S. J., and Witiak, D. T. (1992) Modulation of carcinogenicity in 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA) by fluorine substitution: crystal structures of 5- and 6-fluoro regioisomers. Carcinogenesis 13, 1337-1343, and references therein.
20. Harvey, R. G., and Cortez, C. (1997) Fluorine-substituted derivatives of the carcinogenic dihydrodiol and diol epoxide metabolites of 7-methyl-, 12-methyl- and 7,12-dimethylbenz[a]anthracene. Tetrahedron 53, 7101-7118.
21. Baer-Dubowska, W., Nair, R. V., Dubowski, A., Harvey, R. G., Cortez, C., and DiGiovanni, J. (1996) The effect of fluoro substituents on reactivity of 7-methylbenz[a]anthracene diol epoxides. Chem. Res. Toxicol. 9, 722-728.
22. Wood, A. W., Levin, W., Chang, R. L., Conney, A. H., Slaga, T. J., O'Malley, R. F., Newman, M. S., Buhler, D. R., and Jerina, D. M. (1982) Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl and fluorine-substituted benz[a]anthracenes. J. Natl. Cancer Inst. 69, 725-728.
23. Rinderle, S. J., Black, S. D., Sharma, P. K., and Witiak, D. T. (1992) Comparative metabolism in vitro of a novel carcinogenic polycyclic aromatic hydrocarbon, 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene, and its two regioisomeric B-ring fluoro analogs. Cancer Res. 52, 3035-3042.
24. Borosky, G. L. (1999) Theoretical study related to the carcinogenic activity of polycyclic aromatic hydrocarbons. J. Org. Chem. 64, 7738-7744.
25. Borosky, G. L. (2001) Calculations related to the reactivity of polycyclic aromatic hydrocarbon episulfides. Helv. Chim. Acta 84, 3588-3599.
26. Borosky, G. L. (2003) Theoretical study concerning the reativity of imine derivatives of polycyclic aromatic hydrocarbons. J. Comput. Chem. 24, 601-608.
27. Borosky, G. L., and Laali, K. K. (2005) Theoretical study of azapolycyclic aromatic hydrocarbons (aza-PAHs), modelling carbocations from oxidized metabolites and their covalent adducts with representative nucleophiles. Org. Biomol. Chem. 3, 1180-1188.
28. Borosky, G. L., and Laali, K. K. (2005) A computational study of carbocations from oxidized metabolites of dibenzo[a,h]acridine and their fluorinated and methylated derivatives. Chem. Res. Toxicol. 18, 1876-1886.
29. Okazaki, T., Laali, K. K., Zajc, B., Lakshman, M. K., Kumar, S., Baird, W. M., and Dashwood, W.-M. (2003) Stable ion study of benzo[a]-pyrene (BaP) derivatives: 7,8-dihydro-BaP, 9,10-dihydro-BaP and its 6-halo derivatives, 1- and 3-methoxy-9,10-dihydro- BaP-7(8H)-one, as well as the proximate carcinogen BaP 7,8-dihydrodiol and its dibenzoate, combined with a comparative DNA binding study of regioisomeric (1-, 4-, 2-) pyrenylcarbinols. Org. Biomol. Chem. 1, 1509-1516.
30. Laali, K. K., and Hansen, P. E. (1997) Charge delocalization pathways in persistent 1-pyrenyl-, 4-pyrenyl-, and 2-pyrenylmethylcarbenium ions as models of PAH-epoxide ring opening: NMR studies in superacids and AM1 calculations. J. Org. Chem. 62, 5804-5810.
31. + and related α-carbocations/ carboxonium ions: modeling epoxide ring opening in potent carcinogens. J. Org. Chem. 63, 7280-7285.
32. Laali, K. K., Okazaki, T., Kumar, S., and Galembeck, S. E. (2001) Substituent effects and charge delocalization mode in chrysenium, benzo[c]phenanthrenium, and benzo[g]chrysenium cations: a stable ion and electrophilic substitution study. J. Org. Chem. 66, 780-788.
33. Laali, K. K., Okazaki, T., and Harvey, R. G. (2001) First examples of stable arenium ions from large methylene-bridged polycyclic aromatic hydrocarbons (PAHs). Directive effects and charge delocalization mode. J. Org. Chem. 66, 3977-3983.
34. Laali, K. K., Okazaki, T., and Hansen, P. E. (2000) Stable ion study of regioisomeric carboxonium-substituted pyrenium ions: directive effects, charge delocalization mode, and conformational aspects. J. Org. Chem. 65, 3816-3828.
35. Laali, K. K., Okazaki, T., and Coombs, M. M. (2000) Persistent carbocations from bay region methoxy-substituted cyclopenta[a]phenanthrene and its derivatives. A structure/reactivity study. J. Org. Chem. 65, 7399-7405.
36. Laali, K. K., and Okazaki, T. (2002) Review: NMR of persistent carbocations from polycyclic aromatic hydrocarbons (PAHs). Annu. Rep. NMR Spectrosc. 47, 149-214.
37. Laali, K. K. (2004) Stable ion chemistry of polycyclic aromatic hydrocarbons (PAHs); modeling electrophiles from carcinogens. In Carbocation Chemistry (Olah, G. A., and Prakash, G. K. S., Eds.), Chapter 9, Wiley, Hoboken, NJ.
38. Okazaki, T., and Laali, K. K. (2003) A theoretical (DFT, GIAO-NMR, NICS) study of the carbocations and oxidation dications from azulenes, homoazulene, benzazulenes, benzohomoazulenes, and the isomeric azulenoazulenes. Org. Biomol. Chem. 1, 3078-3093.
39. 2+) from benzo[a]pyrene and its nonalternant isomers azulenophenalenes: a theoretical (DFT, GIAO, NICS) study. J. Org. Chem. 69, 510-516.
40. Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Montgomery, J. A., Jr., Vreven, T., Kudin, K. N., Burant, J. C., Millam, J. M., Iyengar, S. S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G. A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J. E., Hratchian, H. P., Cross, J. B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R. E., Yazyev, O., Austin, A. J., Cammi, R., Pomelli, C., Ochterski, J. W., Ayala, P. Y., Morokuma, K., Voth, G. A., Salvador, P., Dannenberg, J. J., Zakrzewski, V. G., Dapprich, S., Daniels, A. D., Strain, M. C., Farkas, O., Malick, D. K., Rabuck, A. D., Raghavachari, K., Foresman, J. B., Ortiz, J. V., Cui, Q., Baboul, A. G., Clifford, S., Cioslowski, J., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R. L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B., Chen, W., Wong, M. W., Gonzalez, C., and Pople, J. A. (2003) Gaussian 03, Revision B.05, Gaussian, Inc., Wallingford, CT.
41. Becke, A. D. (1993) Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648-5652.
42. Lee, C., Yang, W., and Parr, R. G. (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 37, 785-789.
43. Miehlich, B., Savin, A., Stoll, H., and Preuss, H. (1989) Results obtained with the correlation energy density functionals of Becke and Lee, Yang and Parr. Chem. Phys. Lett. 157, 200-206.
44. Glendening, E. D., Reed, A. E., Carpenter, J. E., and Weinhold, F. (2003) NBO Version 3.1, Gaussian, Inc., Wallingford, CT.
45. Cancès, M. T., Mennucci, V., and Tomasi, J. (1997) A new integral equation formalism for the polarizable continuum model: theoretical background and applications to isotropic and anisotropic dielectrics. J. Chem. Phys. 107, 3032-3041.
46. Mennucci, B., and Tomasi, J. (1997) Continuum solvation models: a new approach to the problem of solute's charge distribution and cavity boundaries. J. Chem. Phys. 106, 5151-5158.
47. Mennucci, B., Cancès, E., and Tomasi, J. (1997) Evaluation of solvent effects in isotropic and anisotropic dielectrics and in ionic solutions with a unified integral equation method: theoretical bases, computational implementation, and numerical applications. J. Phys. Chem. B 101, 10506-10517.
48. Tomasi, J., Mennucci, B., and Cancès, E. (1999) The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level. J. Mol. Struct.: THEOCHEM 464, 211-226.
49. Dewar, M. J. S., Zoebisch, E. G., Healy, E. F., and Stewart, J. J. P. (1985) Development and use of quantum mechanical molecular models. 76. AMI: a new general purpose quantum mechanical molecular model. J. Am. Chem. Soc. 107, 3902-3909.
50. Islam, N. B., Whalen, D. L., Yagi, H., and Jerina, D. M. (1987) pH dependence of the mechanism of hydrolysis of benzo[a]pyrene-cis-7,8-diol 9,10-epoxide catalyzed by DNA, poly(G), and poly(A). J. Am. Chem. Soc. 109, 2108-2111.
51. Gupta, S. C., Islam, N. B., Whalen, D. L., Yagi, H., and Jerina, D. M. (1987) Bifunctional catalysis in the nucleotide-catalyzed hydrolysis of (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene. J. Org. Chem. 52, 3812-3815.
52. Nashed, N. T., Bax, A., Loncharich, R. J., Sayer, J. M., and Jerina, D. M. (1993) Methanolysis of K-region arene oxides: comparison between acid-catalyzed and methoxide ion addition reactions. J. Am. Chem. Soc. 115, 1711-1722.
53. Nashed, N. T., Balani, S. K., Loncharich, R. J., Sayer, J. M., Shipley, D. Y., Mohan, R. S., Whalen, D. L., and Jerina, D. M. (1991) Solvolysis of K-region arene oxides: substituent effects on reactions of benz[a]anthracene 5,6-oxide. J. Am. Chem. Soc. 113, 3910-3919.
54. Nashed, N. T., Rao, T. V. S., and Jerina, D. M. (1993) Sterically induced methoxyl migration on acid-catalyzed dehydration of K-region trans-dihydrodiol monomethyl ethers. J. Org. Chem. 58, 6344-6348.
55. Utesch, D., Glatt, H., and Oesch, F. (1987) Rat hepatocyte-mediated bacterial mutagenicity in relation to the carcinogenic potency of benz[a]anthracene, benzo[a]pyrene, and twenty-five methylated derivatives. Cancer Res. 47, 1509-1515, and references therein.
56. Afshar, C. E., Katz, A. K., Carrell, H. L., Amin, S., Desai, D., and Glusker, J. P. (1999) Three-dimensional structure of anti-5,6-dimethylchrysene- 1,2-dihydrodiol-3,4-epoxide: a diol epoxide with a bay region methyl group. Carcinogenesis 20, 1549-1553.
57. Cavalieri, E. L., and Rogan, E. G. (1992) The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. Pharmacol. Ther. 55, 183-194.
58. Cavalieri, E. L., and Rogan, E. G. (1995) Central role of radical cations in metabolic activation of polycyclic aromatic hydrocarbons. Xenobiotica 25, 677-688.
59. Cavalieri, E. L., Roth, R., and Rogan, E. G. (1976) Metabolic activation of aromatic hydrocarbons by one-electron oxidation in relation to the mechanism of tumor initiation. In Polycyclic Aromatic Hydrocarbons: Chemistry, Metabolism, and Carcinogenesis (Freudnthal, R. I., and Jones, P. W., Eds.) Vol. 1, pp 181-190, Raven Press, New York.
60. RamaKrishna, N. V. S., Cavalieri, E. L., Rogan, E. G., Dolnikowski, G., Cerny, R. L., Gross, M. L., Jeong, H., Jankowiak, R., and Small, G. J. (1992) Synthesis and structure determination of the adducts of the potent carcinogen 7,12-dimethylbenz[a]anthracene and deoxyribonucleosides formed by electrochemical oxidation: models for metabolic activation by one-electron oxidation. J. Am. Chem. Soc. 114, 1863-1874.
61. Flesher, J. W., and Sydnor, K. L. (1971) Carcinogenicity of derivatives of 7,12-dimethylbenz[a]anthracene. Cancer Res. 31, 1951-1954.
62. Flesher, J. W., and Sydnor, K. L. (1973) Possible role of 6-hydroxymethylbenzo[a]pyrene as a proximate carcinogen of benzo[a]pyrene and 6-methylbenzo[a]pyrene. Int. J. Cancer 11, 433-437.
63. Surh, Y. J., Liem, A., Miller, E. C., and Miller, J. A. (1989) Metabolic activation of the carcinogen 6-hydroxymethylbenzo[a]pyrene: formation of an electrophilic sulfuric acid ester and benzylic DNA adducts in rat liver in vivo and in reaction in vitro. Carcinogenesis 10, 1519-1528.
64. Flesher, J. W., Horn, J., and Lehner, A. F. (1997) 7-Sulfooxy-methyl-12- methylbenz[a]anthracene is an exceptionally reactive electrophilic mutagen and ultimate carcinogen. Biochem. Biophys. Res. Commun. 231, 144-148.
65. Flesher, J. W., Horn, J., and Lehner, A. F. (1997) 6-Sulfooxy- methylbenzo[a]pyrene is an ultimate electrophilic and carcinogenic form of the intermediary metabolite 6-hydroxymethylbenzo[a]pyrene. Biochem. Biophys. Res. Commun. 234, 554-558.
66. Flesher, J. W., Horn, J., and Lehner, A. F. (2004) Formation of benzylic alcohols and meso-aldehydes by one electron oxidation of DMBA, a model for the first metabolic step in methylated carcinogenic hydrocarbon activation. Polycyclic Aromat. Compd. 24, 501-511.
67. Laali, K. K., and Hansen, P. E. (1993) Generation and NMR studies of persistent fluoro(alkyl)pyrenium ions and their tetrahydro and hexahydro derivatives in superacid media. J. Org. Chem. 58, 4096-4104.
68. Laali, K. K., Tanaka, M., and Hansen, P. E. (1998) First examples of fluorinated and chlorinated polycyclic aromatic hydrocarbon (PAH) dications from benzo[a]pyrene, pyrene, and their alkyl-substituted derivatives. J. Org. Chem. 63, 8217-8223.
69. Dipple, A. (1994) Reactions of polycyclic aromatic hydrocarbons with DNA. In DNA Adducts: Identification and Biological Significance (Hemminki, K., Dipple, A., Shuker, D. E. G., Kadlubar, F. F., Segerback, D., and Bartsch, H., Eds.) IARC Publications, Lyon, France.
70. Cavalieri, E. L., and Rogan, E. G. (1998) Mechanism of tumor initiation by polycyclic aromatic hydrocarbons in mammals. In The Handbook of Environmental Chemistry: PAHs and Related Compounds (Neilson, A. H., Ed.) Vol. 3J, pp 81-117, Springer, Heidelberg, Germany.
71. 32P-postlabeled rat mammary DMBA-DNA adducts. Carcinogenesis 11, 1959-1963.
72. Agarwal, S. K., Sayer, J. M., Yeh, H. J. C., Pannell, L. K., Hilton, B. D., Pigott, M. A., Dipple, A., Yagi, H., and Jerina, D. M. (1987) Chemical characterization of DNA adducts derived from the configurationally isomeric benzo[c]phenanthrene-3,4-diol 1,2-epoxides J. Am. Chem. Soc. 109, 2497-2504, and references therein.