Molecular modeling of four stereoisomers of the major B[a]PDE adduct (at N2-dG) in five cases where the structure is known from NMR studies: Molecular modeling is consistent with NMR results

Chemical Research in Toxicology

Volumn 15, Issue 11, 2002, Pages 1429-1444

  Lee, Chiu Hong ^a   Chandani, Sushil ^a   Loechler, Edward L ^a  

^a Boston University   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

7,8,9,10 TETRAHYDRO 7,8 DIHYDROXYBENZO[A]PYRENE 9,10 OXIDE; BENZO[A]PYRENE DERIVATIVE; CARCINOGEN; DNA POLYMERASE; MUTAGENIC AGENT; POLYCYCLIC AROMATIC HYDROCARBON; UNCLASSIFIED DRUG; BENZO[A]PYRENE; DNA; DRUG DERIVATIVE;

AMINO ACID SEQUENCE; ARTICLE; CHEMICAL MUTAGENESIS; CHEMICAL STRUCTURE; CONFORMATION; DNA ADDUCT; DNA REPLICATION; ENERGY METABOLISM; GENE MUTATION; HYPOTHESIS; METABOLIC REGULATION; MOLECULAR DYNAMICS; MOLECULAR MODEL; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PROTEIN CONFORMATION; RELIABILITY; SIMULATION; STEREOISOMERISM; CHEMISTRY; MUTAGENESIS; STRUCTURE ACTIVITY RELATION;

BENZO(A)PYRENE; DNA; DNA ADDUCTS; MAGNETIC RESONANCE SPECTROSCOPY; MODELS, MOLECULAR; MUTAGENESIS; NUCLEIC ACID CONFORMATION; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0036851728     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx0200257     Document Type: Article

References (69)

1. Harvey, R. G. (1997) Polycyclic Aromatic Hydrocarbons: Chemistry and Cancer, Wiley-VCH, New York.
2. Phillips, D. H. (1983) Fifty years of benzo[a]pyrene. Nature 303, 468-472.
3. Singer, B., and Grunberger, D. (1983) Molecular Biology of Mutagens and Carcinogens, Plenum Press, New York.
4. Conney, A. H. (1982) Induction of microsomal enzymes by foreign chemicals and carcinogens by polycyclic aromatic hydrocarbons. Cancer Res. 42, 4875-4917.
5. Dipple, A. (1985) Polycyclic aromatic hydrocarbon carcinogens. In Polycyclic Aromatic Hydrocarbons and Carcinogenesis (Harvey, R. G., Ed.) pp 1-17, American Chemical Society Press, Washington, DC.
6. Jones, P. W. (1982) Polynuclear aromatic hydrocarbons. In Handbook of Carcinogens and Hazardous Substances (Bowman, M. G., Ed.) pp 573-639, Marcel Dekker, New York.
7. Grasso, P. (1984) Carcinogens in food. In Chemical Carcinogens (2nd Ed.) (Searle, C. E., Ed.) ACS Monograph 182, pp 1205-1239, American Chemical Society Press, Washington, DC.
8. Cheng, S. C., Hilton, B. D., Roman, J. M., and Dipple, A. (1989) DNA adducts from carcinogenic and noncarcinogenic enantiomers of benzo[a]pyrene dihydrodiol epoxide. Chem. Res. Toxicol. 2, 334-340.
9. Sayer, J. M., Chadha, A., Agarwal, H. S. K., Yeh, H. J. C., Yagi, H., and Jerina, D. M. (1991)Covalent nucleoside adducts of benzo-[a]pyrene 7,8-diol 9,10-epoxides: Structural reinvestigation and characterization of a novel adenosine adduct on the ribose moiety. J. Org. Chem. 56, 20-29.
10. Eisenstadt, E., Warren, A. J., Porter, J., Atkins, D., and Miller, J. H. (1982) Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions. Proc. Natl. Acad. Sci. U.S.A. 82, 1945-1949.
11. Bernelot-Moens, C., Glickman, B. W., and Gordon, A. J. E. (1990) Induction of specific frameshift and base substitution events by benzo[a]pyrene diol epoxide in excision-repair-deficient Escherichia coli. Carcinogenesis 11, 781-785.
12. Yang, J. L., Maher, V. M., and McCormick, J. J. (1987) Kinds of mutations formed when a human shuttle vector containing adducts of (±)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9, 10-dihydrobenzo[a]pyrene replicates in human cells. Proc. Natl. Acad. Sci. U.S.A. 84, 3787-3791.
13. Yang, J.-L., Chen, R.-H., Maher, V. M., and McCormick, J. J. (1990) Kinds and locations of mutations induced by (±)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9, 10-dihydro-benzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in diploid human fibroblasts. Carcinogenesis 12, 71-75.
14. Carothers, A. M., and Grunberger, D. (1990) DNA base changes in benzo[a]pyrene diol epoxide-induced dihydrofolate reductase mutants of Chinese hampster ovary cells. Carcinogenesis 11, 189-192.
15. Rodriguez, H., and Loechler, E. L. (1993) Mutational spectra of the (+)-anti-diol epoxide of benzo[a]pyrene in a supF gene of an Escherichia coli plasmid: DNA sequence context influences hotspots, mutational specficity and the extent of SOS enhancement of mutagenesis. Carcinogenesis 14, 373-383.
16. Rodriguez, H., and Loechler, E. L. (1993) Mutagenesis by the (+)- anti-diol epoxide of benzo[a]pyrene: What controls mutagenic specificity? Biochemistry 32, 373-383.
17. Wei, S.-J. C., Chang, R. L., Wong, C.-Q., Bhachech, N., Cui, X. X., Hennig, E., Yagi, H., Sayer, J. M., Jerina, D. M., Preston, B. D., and Conney, A. H. (1991) Dose-dependent differences in the profile of mutations induced by an ultimate carcinogen from benzo[a]pyrene Proc. Natl. Acad. Sci. U.S.A. 88, 11227-11230.
18. Wei, S.-J. C., Chang, R. L., Bhachech, N., Cui, X. X., Merkler, K. A., Wong, C. Q., Hennig, E., Yagi, H., Jerina, D. M., and Conney, A. H. (1993) Dose-dependent differences in the profile of mutations induced (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetra-hydrobenzo[a]pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in Chinese hampster V79 cells. Cancer Res. 53, 3294-3301.
19. Wei, S. J., Chang, R. L., Hennig, E., Cui, X. X., Merkler, K. A., Wong, C. Q., Yagi, H., Jerina, D. M., and Conney, A. H. (1995) Mutagenic selectivity at the HPRT locus in V-79 cells: Comparison of muattions caused by bay-region benzo[a]pyrne 7,8-diol-9,10-opxide enantiomers with high and low carcinmogenic activity. Carcinogenesis 15, 1729-1735.
20. Wei, S. J., Chang, R. L., Wong, C. Q., Cui, X. X., Dandamudi, N., Lu, Y. P., Merkler, K. A., Sayer, J. M., Conney, A. H., and Jerina, D. M. (1999) The ratio of deoxyadenosine to deoxyguanosine adducts formed by (+)-(7R,8S,9S,10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in purified calf thymus DNA and DNA in V-79 cells is independent of dose. Int. J. Oncol. 14, 509-513
21. 2-Gua, when studied in an Escherichia coli plasmid using site-directed methods. Carcinogenesis 13, 1415-1425.
22. 2-dG adduct of (+)-anti-B[a]PDE shows a dramatically different mutagenic specificity (predominantly, G → A) in a 5′-CGT-3′ sequence context. Biochemistry 36, 10256-10261.
23. 2-dG adducts of B[a]PDE: configuration of the adduct bond is more important than of the hydroxyl groups. Biochemistry 36, 13263-13269.
24. 2-dG adduct of(+)-anti-B[a]PDE induces G → A mutations in a 5≄-AGA-3≄ sequence context. Carcinogenesis 20, 261-268.
25. 2-Gua adduct of the (+)-anti-benzo[a]pyrene diol epoxide is capable of inducing G → A and G → C, in addition to G → T, mutations. Biochemistry 34, 13545-13553.
26. Moriya, M., Spiegel, S., Fernandes, A., Amin, S., Liu, T.-M., Geacintov, N. E., and Grollman, A. P. (1996) Fidelity of translesion synthesis past benzo[a]pyrene diol epoxide-2′-deoxyguanosine DNA adducts: Marked effects of host cell, sequence context, and chirality. Biochemistry 35, 16646-16651.
27. Page, J. E., Zajc, B., Oh-hara, T., Lakshman, M. K., Sayer, J. M., Jerina, D. M., and Dipple, A. (1998) Sequence context profoundly influences the mutagenic potency oftrans-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-purine nucleoside adducts in site-specific mutation studies. Biochemistry 37, 9127-9137.
28. 6 at the second position of N-ras codon 61. J. Biol. Chem. 270, 4990-5000.
29. 6 is dependent on both chirality of the lesion and the local sequence context. J. Biol. Chem. 268, 23427-23434.
30. 2-2′-deoxyguanosine adducts in Escherichia coli and simian kidney cells. Biochemistry 37, 10164-10172.
31. Loechler, E. L. (1995) How are potent bulky carcinogens able to induce such a diverse array of mutations? Mol. Carcinog. 13, 213-219.
32. Seo, K.-Y., Jelinsky, S. A., and Loechler, E. L. (2000) Adduct conformational complexity causes adduct mutational complexity: Evidence from mutagenic studies of the potent environmental carcinogen benzo[a]pyrene. Mutat. Res. 463, 215-245.
33. Fountain M. A., and Krugh T. R. (1995) Structural characterization of a (+)-trans-anti-benzo[a]pyrene-DNA adduct using NMR, restrained energy minimization and molecular dynamics. Biochemistry 34, 3152-3161.
34. Cosman M., de los Santos C., Fiala, R., Hingerty, B. E., Ibanez, V., Margulis, L. A., Live, D., Geacintov, N. E., Broyde, S., and Patel, D. J. (1992) Solution conformation of the major adduct between the carcinogen (+)-anti-benzo[a]pyrene diol epoxide and DNA. Proc. Natl. Acad. Sci. U.S.A. 89, 1914-1918.
35. Geacintov, N. E., Cosman, M., Hingerty, B. E., Amin, S., Broyde, S., and Patel, D. J. (1997) NMR solution structures of stereoisomeric polycyclic aromatic carcinogen-DNA adducts: Principles, patterns and diversity. Chem. Res. Toxicol. 10, 111-131.
36. Suh, M., Jankowiak, R., Ariese, F., Mao, B., Geacintov, N. E., and Small, G. J. (1994) Flanking base effects on the structural conformation of the (+)-trans-anti-benzo[a]pyrene diolepoxide adduct to N-2-dG in sequence-defined oligonucleotides Carcinogenesis 15, 2891-2898.
37. Marsch, G. A., Jankowiak, R., Suh, M., and Small, G. J. (1994) Sequence dependence of benzo[a]pyrene diol epoxide-DNA adduct conformation distribution: A study by laser-induced fluorescence/polyacrylamide gel electrophoresis. Chem. Res. Toxicol. 7, 98-109.
38. LeBreton, P. E., Huang, C.-R., Fernando, H., Zajc, B., Lakshman, M. K., Sayer, J. M., and Jerina, D. M. (1995) Multiple fluorescence lifetimes for oligonucleotides containing single, site-specific modifications at guanines and adenines corresponding to trans addition of the exocyclic amino groups to (+)-(7R,8S,9S,10R)- and (-)-(7S,8R,9R,10S)-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydro-benzo[a]pyrene Chem. Res. Toxicol. 8, 338-348.
39. de los Santos, C., Cosman, M., Hingerty B., Ibanez, V., Margulis, L. A., Geacintov, N. E., Broyde, S., and Patel, D. J. (1992) Influence of benzo[a]pyrene diol epoxide chirality on solution conformations of DNA covalent adducts: The (-)-trans-anti-[BP]G·C adduct structure and comparison with the (+)-trans-anti-[BP]G·C enantiomer. Biochemistry 31, 5245-5252.
40. Cosman, M., de los Santos, C., Fiala, R., Hingerty, B. E., Ibanez, V., Luna, E., Harvey, R., Geacintov, N. E., Broyde, S., and Patel, D. J. (1993) Solution conformation of the (+)-cis-anti-[BP]dG adduct in a DNA duplex: Intercalation of the covalently attached benzo[a]pyrenyl ring into the helix and displacement of the modified deoxyguanosine. Biochemistry 32, 4145-4155.
41. Cosman, M., Hingerty, B. E., Luneva, N., Amin, S., Geacintov, N. E., Broyde, S., and Patel, D. J. (1996) Solution conformation of the (-)-cis-anti-Benzo[a]pyrenyl-dG adduct opposite dC in a DNA duplex: intercalation of the covalently attached BP ring into the helix with base displacement of the modified deoxyguanosine into the major groove. Biochemistry 35, 9850-9863.
42. 6-substituted deoxyguanosine adduct of 1-naphthylamine in the DNA double helix. Chem.-Biol. Interact. 22, 329-229.
43. Kadlubar, F. F. (1980) A trascersion mutation hypothesis for chemical carcigensesis by N2-substitution of guanine in DNA. Chem.-Biol. Interact. 31, 255-263.
44. Drinkwater, N., Miller J. A., and Miller, E. C., and Yang, N.-C. (1978) Covalent intercalative binding to DNA in relation to mutagenicity of hydrocarbon epoxides and N-acetoxy-2-acetyl-aminofluorene. Cancer Res. 38, 3247-3255.
45. Hogan, M. E., Dattagupta, N., and Whitlock, J. P., Jr. (1981) Carcinogen-induced alteration of DNA structure. J. Biol. Chem. 256, 4504-4513.
46. Taylor, E. R., Miller, K. J., and Bleyer, A. J. (1983) Interactions of molecules with nucleic acids. X. Covalent intercalative binding of the carcinogeic BPDE I (+) to kinked DNA. J. Biomol. Struct. Dyn. 1, 883-903.
47. Miller, K. J., Taylor, E. R., and Dommen, J. (1985) A mechanism for the stereoselectivity and binding of benzo[a]pyrene diol epoxides to DNA. In Polycyclic Aromatic Hydrocarbons and Carcinogens (Harvey. R. G., Ed.) ACS Symposium Series 283, pp 239-288, American Chemical Society, Washington, DC.
48. Aggarwal, A. K., Islam, S. A., and Neidle, S. (1983) Computer modelling studies of the covalent interactions between DNA and the enantiomers of anti-7,8-diol,9,10-epoxybenzo[a]pyrene. J. Biomol. Struct. Dyn. 1, 873-881.
49. Anderson, R. W., Whitlow, M. D., Teeter, M. M., and Mohr, S. C. (1987) A-DNA accommodates adducts derived from diol epoxides of polycyclic aromatic hydrocarbons bound in a "side-stackeing" mode. J. Biomol. Struct. Dyn. 5, 383-404.
50. Neidle, S., Pearl, L., and Beveridge, A. (1987) A crystallographic and molecular modelling studies of carcinogen-DNA interactions. Molecular Mechanisms of Carcinogenic and Antitumor Activity. Pontif. Acad. Sci. Scr. Varia 70, 67-93.
51. Zakrzewska, K., and Pullman, B. (1987) Sequence slectivity, a test of the nature of the covalent adduct formed between benzo-[a]pyrene and DNA. J. Biomol. Struct. Dyn. 4, 845-858.
52. Rao, S. N., Lybrand, T., Michaud, D., Jerina, D. M., and Kollman, P. A. (1989) Molecular mechanics simulations of covalent complexes between polycyclic carcinogens and B-DNA. Carcinogenesis 10, 27-38.
53. Weston, A., Newman, M., Mann, D., and Brooks, B. (1990) Molecular mechanisms and antibody binding in the structural analysis of polycyclic aromatic hydrocarbon-diol-epoxide-DNA adducts. Carcinogenesis 11, 859-864.
54. Loechler, E. L. (1991) Molecular modeling in mutagenesis and carcinogenesis. Methods in Enzymology, Molecular Design and Modeling: Concepts and Applications, Vol. 203, pp 458-476.
55. Singh, S. B., Hingerty, B. E., Singh, U. C., Greenberg, S. P., Geacintov, N. E., and Broyde, S. (1991) Structure of the (+)- and (-)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo-[a]pyrene adducts to guanine-N2 in a duplex dodecamer. Cancer Res. 51, 3482-3492.
56. Xie, X. M., Geacintov, N. E., and Broyde, S. (1999) Origins of conformational differences between cis and trans DNA adducts derived from enantiomeric anti-benzo[a]pyrene diol epoxides. Chem Res Toxicol. 12, 597-609
57. Kozack, R., and Loechler, E. L. (1997) Molecular modeling of the conformational complexity of (+)-anti-B[a]PDE-adducted DNA using simulated annealing. Carcinogenesis 18, 1585-1593.
58. 2-dG) in the eight conformations and the five DNA sequences most relevant to base substitution mutagenesis. Carcinogenesis 20, 85-94.
59. 2-dG) Causes G → T vs G → A Mutations Based Upon a Correlation between Mutagenesis and Molecular Modeling Results. Carcinogenesis 20, 95-104.
60. 2-dG) of the potent environmental carcinogen, benzo[a]pyrene. Mutat. Res. 450, 41-59.
61. InsightII, version 98.0 (1998) Molecular Simulation Inc., San Diego.
62. Nilsson, L., and Karplus, M. (1986) Empirical energy functions for energy minimization and dynamics of nucleic acids. J. Comput. Chem. 7, 591-616.
63. 6-methylguanine: The syn- and anti-conformers can be of similar energies in duplex DNA as estimated by molecular modeling techniques. Carcinogenesis 12, 1693-1699.
64. Arnott, S., Campbell Smith, P. J., and Chandraselaran, R. (1975) Atomic coordinates and molecular conformations for DNA-DNA, RNA-RNA, and DNA-RNA helices. In Handbook of Biochemistry and Molecular Biology, Vol. II: Nucleic Acids (Fasman, G. D., Ed.) pp 411-422, 3rd ed., CRC Press, Cleveland.
65. Saenger, W. (1984) Principles of nucleic acid structure, Springer-Verlag, New York.
66. Xie X. M., Geacintov, N. E., and Broyde, S. (1999) Stereochemical origin of opposite orientations in DNA adducts derived from enantiomeric anti-benzo[a]pyrene diol epoxides with different tumorigenic potentials. Biochemistry 38, 2956-2968.
67. Yan, S., Shapiro, R., Geacintov, N. E., and Broyde, S. (2001) Stereochemical, structural, and thermodynamic origins of stability differences between stereoisomeric benzo[a]pyrene adducts. J. Am. Chem. Soc. 123, 7054-7066.
68. Wang, L., Hingerty, B. E., Srinivasan, A. R., Olson, W. K., and Broyde S. (2002) Accurate representation of B-DNA double helical structure with implicit solvent and counterions. Biophys J. 83, 382-406.
69. Kollman, P. A., Massova, I., Reyes, C., Kuhn, B., Huo, S., Chong, L., Lee, M., Lee, T., Duan, Y., Wang, W., Donini, O., Cieplak, P., Srinivasan, J., Case, D. A., and Cheatham, T. E., 3rd (2000) Calculating structures and free energies of complex molecules: Combining molecular mechanics and continuum models. Acc. Chem. Res. 33, 889-897.