Quantum chemical studies on ultimate carcinogenic metabolites from polycyclic aromatic hydrocarbons

Current Medicinal Chemistry

Volumn 15, Issue 28, 2008, Pages 2901-2920

  Borosky, Gabriela L ^a  

^a DEPARTAMENTO DE FISICOQUÍMICA   (Argentina)

Author keywords

Aromatic amines; Carbocations; DNA covalent adducts; Mutagenic carcinogenic metabolites; Polycyclic aromatic hydrocarbons; Quantum chemical calculations

Indexed keywords

AMINE; AROMATIC AMIDE; AROMATIC COMPOUND; CARCINOGEN; CYTOSINE; ENVIRONMENTAL CHEMICAL; GUANINE; POLYCYCLIC AROMATIC HYDROCARBON DERIVATIVE; EPOXIDE; POLYCYCLIC AROMATIC HYDROCARBON; SOLVENT;

CARCINOGENICITY; CHEMICAL ANALYSIS; CHEMICAL INTERACTION; CHEMICAL MODIFICATION; CHEMICAL REACTION; CHEMICAL STRUCTURE; COVALENT BOND; DNA ADDUCT; DNA BINDING; DNA CONFORMATION; DNA DETERMINATION; GENE MUTATION; HYDROGEN BOND; HYDROPHOBICITY; METABOLITE; METHYLATION; MUTAGENICITY; OXIDATION; PROTON TRANSPORT; QUANTUM CHEMISTRY; REVIEW; SOLVATION; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; SYNTHESIS; THERMODYNAMICS; THERMOSTABILITY; ANIMAL; CHEMICAL MODEL; CHEMISTRY; COMPUTER PROGRAM; CONFORMATION; HUMAN; PH; POLLUTANT; QUANTUM THEORY;

AMINES; ANIMALS; CARCINOGENS; DNA ADDUCTS; ENVIRONMENTAL POLLUTANTS; EPOXY COMPOUNDS; HUMANS; HYDROGEN-ION CONCENTRATION; MODELS, CHEMICAL; MOLECULAR CONFORMATION; POLYCYCLIC HYDROCARBONS, AROMATIC; QUANTUM THEORY; SOFTWARE; SOLVENTS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 58149383067     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986708786848686     Document Type: Review

References (114)

1. International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans, Vol. 32: Polycyclic Aromatic Compounds, Part 1, Chemical Environmental and Experimental Data, IARC: Lyon, 1983.
2. Harvey, R.G. Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogenicity, Cambridge University Press: Cambridge, UK, 1991.
3. Harvey, R.G. Polycyclic Aromatic Hydrocarbons, Wiley-VCH: New York, 1997.
4. Wood, A.W.; Chang, R.L.; Levin, W.; Ryan, D.E.; Thomas, P.E.; Croisy-Delcey, M.; Ittah, Y.; Yagi, H.; Jerina, D.M.; Conney, A.H. Mutagenicity of the dihydrodiols and bay-region diol-epoxides of benzo(c)phenanthrene in bacterial and mammalian cells. Cancer Res., 1980, 40, 2876-2883 and references therein.
5. Jerina, D.M.; Yagi, H.; Lehr, R.E.; Thakker, D.R.; Schafer-Ridder, M.; Karle, J. M.; Levin, W.; Wood, A.W.; Chang, R.L.; Conney, A.H. In Polycyclic Hydrocarbons and Cancer; Gelboin, H.V.; T'so, P.O.P., Eds.; Academic Press: New York, 1978; Vol. 1, pp. 173-188.
6. Wood, A.W.; Levin, W.; Chang, R.L.; Yagi, H.; Thakker, D.R.; Lehr, R.E.; Jerina, D.M.; Conney, A.H. In Polycyclic Aromatic Hydrocarbons; Jones, P.W., Leber, P., Eds.; Ann Harbor Science Publishers, Inc.: Ann Harbor, MI, 1979; pp. 531-551.
7. Xue, W.; Warshawsky, D. Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: A review. Toxicol. Appl. Pharmacol., 2005, 206, 73-93.
8. Islam, N.B.; Whalen, D.L.; Yagi, H.; Jerina, D.M. 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., 1987, 109, 2108-2111.
9. Gupta, S.C.; Islam, N.B.; Whalen, D.L.; Yagi, H.; Jerina, D.M. Bifunctional catalysis in the nucleotide-catalyzed hydrolysis of (±)- 7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene. J. Org. Chem., 1987, 52, 3812-3815.
10. Nashed, N.T.; Bax, A.; Loncharich, R.J.; Sayer, J.M.; Jerina, D.M. Methanolysis of K-region arene oxides: Comparison between acidcatalyzed and methoxide ion addition reactions. J. Am. Chem. Soc., 1993, 115, 1711-1722.
11. Nashed, N.T.; Balani, S.K.; Loncharich, R.J.; Sayer, J.M.; Shipley, D.Y.; Mohan, R.S.; Whalen, D.L.; Jerina, D.M. Solvolysis of Kregion arene oxides: Substituent effects on reactions of benz[a]anthracene 5,6-oxide. J. Am. Chem. Soc., 1991, 113, 3910.
12. Nashed, N.T.; Rao, T.V.S.; Jerina, D.M. Sterically induced methoxyl migration on acid-catalyzed dehydration of K-region trans-dihydrodiol monomethyl ethers. J. Org. Chem., 1993, 58, 6344-6348.
13. Hecht, S.S.; Melikian, A.A.; Amin, S. In Polycyclic Aromatic Hydrocarbon Carcinogenesis: Structure-Activity Relationships; Yang, S.K.; Silverman B.D., Eds.; CRS Press: Boca Raton, FL, 1988; Vol 1, pp. 95-128.
14. Hecht, S.S.; Amin, S.; Melikian, A.A.; LaVoie, E.J.; Hoffman, D. In Polycyclic Hydrocarbons and Carcinogenesis; Harvey, R. G., Ed.; ACS Symposium Series 283; American Chemical Society: Washington, DC, 1985; Ch. 2, pp. 85-105.
15. Biological Effects of Atmospheric Pollutants, Committee on Biologic Effects of Atmospheric Pollutants, Particulate Polycyclic Organic Matter; National Academy of Sciences: Washington, DC, 1972.
16. Lehr, R.E.; Wood, A.W.; Levin, W.; Conney, A.H.; Jerina, D.M. In Polycyclic Aromatic Hydrocarbon Carcinogenesis: Structure- Activity Relationships; Yang, S.K.; Silverman, B.D., Eds.; CRC Press: Boca Raton, FL, 1988; L. 1, pp. 31-58 and references therein.
17. Chang, R.L.; Wood, A.W.; Xie, J.G.; Huang, M.T.; Cui, X.; Kole, P.L.; Sikka, H.C.; Balani, S.K.; Jerina, D.M.; Kumar S.; Conney, A.H. High tumor-initiating activity of the bay-region (+)- [10R,11S]-dihydrodiol of dibenz[a,h]acridine on mouse skin. Proc. Am. Assoc. Cancer Res., 1996, 37, 128.
18. Warshawsky, D. Environmental sources, carcinogenicity, mutagenicity, metabolism and DNA binding of nitrogen and sulfur heterocyclic aromatics. J. Environ. Sci. Health, 1992, C10, 1-71.
19. Garner, R.C.; Martin, C.N.; Clayson , D.B. In Chemical Carcinogens; Searle, C.E., Ed.; American Chemical Society Monogr. 182: Washington, DC, 1982; Vol. 1, pp. 175-276.
20. Later, D.W.; Pelroy, R.A.; Stewart, D.L.; McFall, T.; Both, G.M.; Lee, M.L.; Tedjamulia, M.; Castle, R. N. Microbial mutagenicity of isomeric two-, three, and four-rings amino polycyclic aromatic hydrocarbons. Env. Mutagen., 1984, 6, 497-515.
21. Adamson, R.H.; Farb, A.; Virmani, R.; Snyderwine, E.G.; Thorgeirsson, S.S.; Takayama, S.; Sugimura, T.; Dalgard, D.W.; Thorgeirsson, U.P. In Heterocyclic Amines in Cooked Foods: Possible Human Carcinogens (23rd Intl. Symp. Princess Takamatsu Cancer Res. Fund); Adamson, R.H.; Gustafsson, J.-A.; Ito, N.; Nagao, M.; Sugimura, T.; Wakabayashi, K.; Yamazoe, Y., Eds.; Princeton Scientific Publishing Co. Inc.: Princeton, NJ, 1995; pp. 260-627.
22. Felton, J.S.; Wu, R.; Knize, M.G.; Thompson, L.H.; Hatch, F.T. In Heterocyclic Amines in Cooked Foods: Possible Human Carcinogens (23rd Intl. Symp. Princess Takamatsu Cancer Res. Fund); Adamson, R.H.; Gustafsson, J.-A.; Ito, N.; Nagao, M.; Sugimura, T.; Wakabayashi, K.; Yamazoe, Y., Eds.; Princeton Scientific Publishing Co. Inc.: Princeton, NJ, 1995, pp. 50-58.
23. Felton, J.S.; Knize, M.G.; Hatch, F.T.; Tanga, M.J.; Colvin, M.E. Heterocyclic amine formation and the impact of structure on their mutagenicity. Cancer Lett., 1999, 143, 127-134
24. Sugimura, T. Overview of carcinogenic heterocyclic amines. Mutat. Res., 1997, 376, 211-219.
25. Schut, H.A.J.; Snyderwine, E.G. DNA adducts of heterocyclic amine food mutagens: Implications for mutagenesis and carcinogenesis. Carcinogenesis, 1999, 20, 353-368.
26. Weisburger, J.H. Comments on the history and importance of aromatic and heterocyclic amines in public health. Mutat. Res., 2002, 506/507, 9-20.
27. Kadlubar, F.F.; Beland, F.A. In Polycyclic Hydrocarbons and Carcinogenesis; Harvey, R.G., Ed.; ACS Symposium Series 283, American Chemical Society: Washington, DC, 1985; pp. 341-370
28. Beland, F.A.; Kadlubar, F.F. In Handbook of Experimental Pharmacology; Cooper, C.S.; Grover, P.L., Eds.; Springer-Verlag: Heidelberg, 1990; Vol. 94, Part 1, pp. 267-325.
29. Kadlubar, F.F.; Miller, J.A.; Miller, E.C. Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Cancer Res., 1977, 37, 805-814.
30. Connor, T.H.; Ramanujam, V.M.S.; Rinkus, S.J.; Legator, M.S.; Trieff, N.M. The evaluation of mutagenicities of 19 structurally related aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100. Mutat. Res., 1983, 118, 49-59.
31. Trieff, N.M.; Biagi, G.L.; Ramanujam, V.M.S.; Connor, T.H.; Cantelli-Forti, G.; Guerra, M.C.; Bunce, 3rd, H.; Legator, M.S. Aromatic amines and acetamides in Salmonella typhimurium TA98 and TA100: A quantitative structure-activity relation study. Mol. Toxicol., 1989, 2, 53-65.
32. Borosky, G.L.; Laali, K.K. In Recent Developments in Carbocation and Onium Ion Chemistry; Laali, K.K., Ed; ACS Symposium Series 965, American Chemical Society: Washington, DC, 2007; Chapter 16, pp. 329-363.
33. Borosky, G.L. Theoretical study related to the carcinogenic activity of polycyclic aromatic hydrocarbons. J. Org. Chem., 1999, 64, 7738-7744 and references therein.
34. Harvey, R.G.; Geacintov, N.E. Intercalation and binding of carcinogenic hydrocarbon metabolites to nucleic acids. Acc. Chem. Res., 1988, 21, 66-73 and references therein.
35. Borosky, G.L.; Laali, K.K. Carbocations from oxidized metabolites of benzo[a]anthracene. A computational study of their methylated and fluorinated derivatives and guanine adducts. Chem. Res. Toxicol., 2006, 19, 899-907.
36. Wood, A.W.; Levin, W.; Chang, R.L.; Lehr, R.E.; Schaefer-Ridder, M.; Karle, J.M.; Jerina, D.M.; Conney, A.H. Tumorigenicity of five dihydrodiols of benz[a]anthracene on mouse skin: Exceptional activity of benz[a]anthracene-3,4-diol. Proc. Natl. Acad. Sci. USA, 1977, 74, 3176-3179.
37. Wislocki, P.G.; Fiorentini, K.M.; Fu, P.P.; Yang, S.K.; Lu, A.Y. Tumor-initiating ability of the twelve monomethylbenz [a]anthracenes. Carcinogenesis, 1982, 3, 215-217.
38. Pataki, J.; Huggins, C. Molecular site of substituents of benz[a]anthracene related to carcinogenicity. Cancer Res., 1969, 29, 506-509.
39. Sugiyama, T. Chromosomal aberrations and carcinogenesis by various benz[a]anthracene derivatives. Gann, 1973, 64, 637-639.
40. Huggins, C.B.; Pataki, J.; Harvey, R.G. Geometry of carcinogenic polycyclic aromatic hydrocarbons. Proc. Natl. Acad. Sci. USA, 1967, 58, 2253-2260.
41. Dipple, A.; Moschel, R.C.; Bigger, C.A.H. In Chemical Carcinogens; Searle, C.E., Ed.; ACS Monograph 182, American Chemical Society: Washington, DC, 1984; Vol. 1, pp. 41-163.
42. Amin, S.; Krzeminski, J.; Rivenson, A.; Kurtzke, C.; Hecht, S.S.; El-Bayoumy, K. Mammary carcinogenicity in female CD rats of fjord region diol epoxides of benzo[c]phenanthrene, benzo[g]chrysene and dibenzo[a,l]pyrene. Carcinogenesis, 1995, 16, 1971-1974.
43. Borosky, G.L.; Laali, K.K, unpublished results.
44. DiGiovanni, J.; Decina, P.C.; Diamond, L. 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, 1983, 4, 1045-1049.
45. Diamond, L.; Cherian, K.; Harvey, R.G.; DiGiovanni, J. Mutagenic activity of methyl- and fluoro-substituted derivatives of polycyclic aromatic hydrocarbons in a human hepatoma (HepG2) cell-mediated assay. Mutat. Res., 1984, 136, 65-72.
46. Sawyer, T.W.; Fisher, E.P.; DiGiovanni, J. Skin tumor-initiating activities of 9- and 10-fluoro derivatives of 7- or 12- methylbenz[a]anthracene in SENCAR mice. Carcinogenesis, 1987, 8, 1465-1468.
47. Harvey, R.G.; Dunne, F.B. Multiple regions of metabolic activation of carcinogenic hydrocarbons. Nature, 1978, 273, 566-568.
48. DiGiovanni, J.; Diamond, L.; Singer, J.M.; Daniel, F.B.; Witiak, D.T.; Slaga, T.J. 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, 1982, 3, 651-655.
49. Black, S.D.; Sharma, P.K.; Gallucci, J.C.; Blackburn, A.C.; Downs, J.W.; Rinderle, S.J.; Witiak, D.T. 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, 1992, 13, 1337-1343 and references therein.
50. Harvey, R.G.; Cortez, C. Fluorine-substituted derivatives of the carcinogenic dihydrodiol and diol epoxide metabolites of 7-methyl, 12-methyl- and 7,12-dimethylbenzaanthracene. Tetrahedron, 1997, 53, 7101-7118.
51. Baer-Dubowska, W.; Nair, R.V.; Dubowski, A.; Harvey, R.G.; Cortez, C.; DiGiovanni, J. The effect of fluoro substituents on reactivity of 7-methylbenz[a]anthracene diol epoxides. Chem. Res. Toxicol., 1996, 9, 722-728.
52. Wood, A.W.; Levin, W.; Chang, R.L.; Conney, A.H.; Slaga, T.J.; O'Malley, R.F.; Newman, M.S.; Buhler, D.R.; Jerina, D.M. Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl and fluorines-ubstituted benz[a]anthracenes. J. Natl. Cancer Inst., 1982, 69, 725-728.
53. Rinderle, S.J.; Black, S.D.; Sharma, P.K.; Witiak, D.T. 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., 1992, 52, 3035-3042.
54. Dipple, A. In DNA Adducts: Identification and Biological Significance; Hemminki, K.; Dipple, A.; Shuker, D.E.G.; Kadlubar, F.F.; Segerback, D.; Bartsch, H., Eds.; IARC Publications: Lyon, 1994.
55. Borosky, G.L.; Laali, K. K. Oxidized metabolites from benzo[a]pyrene, benzo[e]pyrene, and aza-benzo[a]pyrenes. A computational study of their carbocations formed by epoxide ring opening reactions. Org. Biomol. Chem., 2007, 5, 2234-2242.
56. Jerina, D.M.; Yagi, H.; Thakker, D.R.; Sayer, J.M.; van Bladeren, P.J.; Lehr, R.E.; Whalen, D.L.; Levin, W.; Chang, R.L.; Wood, A.W.; Conney, A.H. In Foreign Compound Metabolism; Caldwell, J.; Paulson, G.D., Eds.; Taylor and Francis, LTF: London, 1984; pp. 257-266.
57. Chang, R.L.; Levin, W.; Wood, A.W.; Lehr, R.E.; Kumar, S.; Yagi, H.; Jerina, D.M.; Conney, A.H. Tumorigenicity of the diasteromeric bay-region benzoepyrene 9,10-diol-11,12-epoxides in newborn mice. Cancer Res., 1981, 41, 915-918.
58. Gairola; C.; Glass, J.F. Mutagenicity of some fluoro-derivatives of benzoapyrene. Cancer Lett., 1980, 11, 51-56.
59. Chang, R.L.; Wood, A.W.; Conney, A.H.; Yagi, H.; Sayer, J.M.; Thakker, D.R.; Jerina, D.M.; Levin, W. Role of diaxial versus diequatorial hydroxyl groups in the tumorigenic activity of a benzo[a]pyrene bay-region diol epoxide. Proc. Natl. Acad. Sci. USA, 1987, 84, 8633-8636.
60. Gagliano, A.G.; Geacintov, N.E.; Ibanez, V.; Harvey, R.G.; Lee, H.M. Application of fluorescence and linear dichroism techniques to the characterization of the covalent adducts derived from interaction of (±)-trans-9,10-dihydroxy-anti-11,12-epoxy-9,10,11,12- tetrahydrobenzo[e]pyrene with DNA. Carcinogenesis, 1982, 3, 969-976.
61. Wood, A.W.; Levin, W.; Thakker, D.R.; Yagi, H.; Chang, R.L.; Ryan, D.E.; Thomas, P.E.; Dansette, P.M.; Whittaker, N.; Turujman, S.; Lehr, R.E.; Kumar, S.; Jerina, D.M.; Conney, A.H. Biological activity of benzo[e]pyrene. An assessment based on mutagenic activities and metabolic profiles of the polycyclic hydrocarbon and its derivatives. J. Biol. Chem., 1979, 254, 4408-4415 and references therein.
62. MacLeod, M.C.; Levin, W.; Conney, A.H.; Lehr, R.E.; Mansfield, B.K.; Jerina, D.M.; Selkirk, J.K. Metabolism of benzo(e)pyrene by rat liver microsomal enzymes. Carcinogenesis, 1980, 1, 165-173.
63. Kumar, S.; Sikka, H.C.; Dubey, S.K.; Czech, A.; Geddie, N.; Wang, C.-X.; LaVoie, E.J. Mutagenicity and tumorigenicity of dihydrodiols, diol epoxides, and other derivatives of benzo(f)quinoline and benzo(h)quinoline. Cancer Res., 1989, 49, 20-24
64. Lehr, R.E.; Jerina, D.M. Aza-polycyclic aromatic hycrocarbon carcinogenicity: Predictions of reactivity of tetrahydrobenzo ring epoxide derivatives. Tetrahedron Lett., 1983, 24, 27-30.
65. Borosky, G.L.; Laali, K.K. Theoretical study of aza-polycyclic aromatic hydrocarbons (aza-PAHs), modelling carbocations from oxidized metabolites and their covalent adducts with representative nucleophiles. Org. Biomol. Chem., 2005, 3, 1180-1188.
66. Wood, A.W.; Chang, R.L.; Katz, M.; Conney, A.H.; Jerina, D.M.; Sikka, H.C.; Levin, W.; Kumar, S. Mutagenicity of dihydrodiols and diol epoxides of dibenz[a,h]acridine in bacterial and mammalian cells. Cancer Res., 1989, 49, 6981-6984.
67. Kumar, S.; Chang, R.L.; Wood, A.W.; Xie, J.G.; Huang, M.T.; Cui, X.X.; Kole, P.L.; Sikka, H.C.; Balani, S.K.; Conney, A.H.; Jerina, D.M. Tumorigenicity of racemic and optically pure bay region diol epoxides and other derivatives of the nitrogen heterocycle dibenz[a,h]acridine on mouse skin. Carcinogenesis, 2001, 22, 951-955.
68. Chang, R.L.; Levin, W.; Conney, A.H.; Boyd, D.R.; Balani, S.K.; Yagi, H.; Jerina, D.M.; Wood, A.W. Mutagenicity and tumorigenicity of the four optically active bay-region 3,4-diol-1,2-epoxide isomers of dibenz[a,h]anthracene. Proc. Am. Assoc. Cancer Res., 1989, 30, 144.
69. Chang, R.L.; Levin, W.; Wood, A.W.; Shirai, N.; Ryan, A.J.; Duke, C.C.; Jerina, D.M.; Holder, G.M.; Conney, A.H. High tumorigenicity af the 3,4-dihydrodiol of 7-methylbenz[c]acridine on mouse skin and in newborn mice. Cancer Res., 1986, 46, 4552-4555.
70. Borosky, G.L.; Laali, K. K. A computational study of carbocations from oxidized metabolites of dibenzo[a,h]acridine and their fluorinated and methylated derivatives. Chem. Res. Toxicol., 2005, 18, 1876-1886.
71. Lehr, R.E.; Wood, A.W.; Levin, W.; Conney, A.H.; Jerina, D.M. In Polycyclic Aromatic Hydrocarbon Carcinogenesis: Structure-Activity Relationships; Yang, S.K.; Silverman, B.D., Eds.; CRC Press: Boca Raton, FL, 1988; Vol. 1, pp. 31-58 and references therein.
72. Lacassagne, A.; Buu-Hoi, N.P.; Zajdela, F.; Mabille, P. Carcinogenic activity of some isosteric nitrogenous pentacyclic hydrocarbon carcinogens. Compt. Rend., 1964, 258, 3387-3389.
73. Yamada, K.; Suzuki, T.; Kohara, A.;Hayashi, M.; Hakura, A.; Mizutani; T.; Saeki, K. Effect of 10-aza-substitution on benzo[a]pyrene mutagenicity in vivo and in vitro. Mutat. Res., 2002, 521, 187-200 and references therein.
74. Okuda, H.; Shudo, K.; Okamoto, T. Structure of nucleic acid bases in calf thymus DNA modified by the potent mutagen, 10-azabenzo[a]pyrene-4,5-oxide. Chem. Pharm. Bull., 1983, 31, 2924-2927 and references therein.
75. Fukuhara, K.; Hakura, A.; Sera, N.; Tokiwa, H.; Miyata, N. 1- and 3-nitro-6-azabenzo[a]pyrenes and their N-oxides: Highly mutagenic nitrated azaarenes. Chem. Res. Toxicol., 1992, 5, 149-153.
76. Zoller, U.; Shakkour, E.; Pastersky, I. Attempted synthesis and theoretical calculations of the elusive polycyclic arene episulfides. Phosphorus, Sulfur and Silicon, 1994, 95-96, 453-456.
77. Zoller, U. In Small Ring Heterocycles; Hassner, A. Ed.; Wiley Interscience: New York, 1983; pp. 333-630.
78. Zoller, U.; Shakkour, E.; Pastersky, I.; Sklenak, S.; Apeloig, Y. Polycyclic arene episulfides. Attempted synthesis, molecular orbital calculations and comparison with arene oxides. Tetrahedron, 1998, 54, 14283-14300.
79. Yagi, H.; Vepachedu, S.; Sayer, J.M.; Chang, R.L.; Cui, X.-X.; Zoller, U.; Jerina, D.M. Synthesis and properties of bay-region episulfides of benzo[a]pyrene. Polycyclic Aromat. Compd., 1999, 17, 85-94.
80. Zoller U. Three-membered benzylic thia-rings of polycyclic aromatic hydrocarbons: Synthesis, molecular calculations and properties. J. Sulfur Chem., 2004, 25, 2/3, 241-256.
81. Borosky, G.L. Calculations related to the reactivity of polycyclic aromatic hydrocarbon episulfides. Helv. Chim. Acta, 2001, 84, 3588-3599.
82. Bicker, U.; Fischer, W. Enzymatic aziridine synthesis from β-amino-alcohols - a new example of endogenous carcinogen formation. Nature, 1974, 249, 344-345.
83. Ittah, Y.; Shanak, I.; Blum, J. Stable arene imines. J. Org. Chem., 1978, 43, 397-402.
84. Hatta, Y.; Watanabe, M. Enzyme-induced aziridine formation by rat liver microsomes. Biochem. Biophys. Res. Commun., 1983, 110, 220-227.
85. Watanabe, M.; Tonda, K.; Hirata, M.; Yoshiteru, H. Enzyme-induced aziridine formation by isolated hepatocytes. Biochem. Biophys. Res. Commun., 1983, 112, 356-360.
86. Glatt, H.; Ludewig, G.; Platt, K.L.; Waechter, F.; Yona, I.; Ben-Shoshan, S.; Jerushalmy, P.; Blum, J.; Oesch, F. Arene imines, a new class of exceptionally potent mutagens in bacterial and mammalian cells. Cancer Res., 1985, 45, 2600-2607.
87. Glatt, H.; Abu-Shqara, E.; Harvey, R.G.; Blum, J. Mutagenicity of K-region oxides and imines of chrysene, benzo[c]phenanthrene and benzo[g]chrysene in Salmonella typhimurium. Mutat. Res., 1994, 308, 135-141.
88. Glatt, H.; Abu-Shqara, E.; Martiné, U.; Baidossi, W.; Harvey, R.G.; Blum, J. K-region oxides and imines derived from alkylated benz[α]anthracene congeners: Synthesis, stability in aqueous media and mutagenicity. Mutagenesis, 1994, 9, 83-92.
89. Blum, J.; Cohen, Y.; Levin, S.; Katschak, A.; Glatt, H. Resolution of four K-region arene imines and mutagenicity of the optically pure aziridines. J. Heterocyclic Chem., 1998, 35, 39-43.
90. Glatt, H.; Shtelzer, S.; Sheradsky, T.; Blum, J.; Oesch, F. Mutagenicity of N-substituted phenanthrene 9,10-imines in Salmonella typhimurium and Chinese hamster V79 cells. Environ. Mutagen., 1986, 8, 829-837.
91. Stark, A.-A.; Zeiger, E.; Shtelzer, S.; Sheradsky, T.; Lifshitz, Y.; Blum, J. Structure-activity relationships in the mutagenicity of N-substituted derivatives of phenanthrene-9,10-imine. Mutagenesis, 1986, 1, 35-39.
92. Shalom, Y.; Harvey, R.G.; Blum, J. Adducts of phenanthrene 9,10-imine and of benz[a]anthracene 5,6-imine to some nitrogen heterocycles. J. Heterocyclic Chem., 1996, 33, 681-686.
93. Shalom, Y.; Harvey, R.G.; Blum, J. Synthesis of nucleoside adducts of highly mutagenic polycyclic aromatic imines. Tetrahedron, 1999, 55, 10231-10242.
94. Borosky, G.L. Theoretical study concerning the reactivity of imine derivatives of polycyclic aromatic hydrocarbons. J. Comput. Chem., 2003, 24, 601-608.
95. Jacob, J. Sulfur Analogues of Polycyclic Aromatic Hydrocarbons, Cambridge University Press: Cambridge, UK, 1990.
96. Harvery, R.G. In The Handbook of Environmental Chemistry; Neilson, A.H., Ed.; Springer-Verlag: Berlin, 1998; Vol. 1, part 1 and references therein.
97. Kumar, S.; Kim, T.-Y. An improved and regiospecific synthesis of trans-3,4-dihydrodiol metabolite of benzo i b]naphtho[2,1-d]thiophene. J. Org. Chem., 2000, 65, 3883-3884.
98. Misra, B.; Amin, S. Synthesis and mutagenicity of transdihydrodiol metabolites of benzo[b]naphtho[2,1-d]thiophene. Chem. Res. Toxicol., 1990, 3, 93-97.
99. King, L.C.; Kohan, M.J.; Brooks, L.; Nelson, G.B.; Ross, J.A.; Allison, J.; Adams, L.; Desai, D.; Amin, S.; Padgett, W.; Lambert, G.R.; Richard, A.M.; Nesnow, S. An evaluation of the mutagenicity, metabolism, and DNA adduct formation of 5-nitrobenzo[b]naphtho[2,1-d]thiophene. Chem. Res. Toxicol., 2001, 14, 661-671.
100. Kumar, S.; Kumar, A.; Sikka, H.C. Comparative metabolism of phenanthro[3,4-b]thiophene, phenanthro[4,3-b]thiophene and their carbon analog benzo[c]phenanthrene by rat liver microsomes. Polycyclic Aromat. Compd., 2004, 24, 527-536.
101. Kumar, S.; Saravanan, S., Reuben, P.; Kumar, A. Synthesis of trans-dihydrodiol derivatives of phenanthro(3,4-b)thiophene and phenanthro(4,3-b)thiophene. J. Heterocyclic Chem., 2005, 42, 1345-1356.
102. Kumar, S.; Reuben, P.A.; Kumar, A. Synthesis of dihydrodiols of phenanthro[3,4-b]thiophene and phenanthro[4,3-b]thiophene. Polycyclic Aromat. Compd., 2004, 24, 289-295.
103. Laali, K.K.; Chun, J.-H.; Okazaki, T.; Kumar, S.; Borosky, G.L.; Swartz, C. Electrophilic chemistry of thia-PAHs: Stable carbocations (NMR and DFT), S-alkylated onium salts, model electrophilic substitutions (nitration and bromination) and mutagenicity assay. J. Org. Chem., 2007, 72, 8383-8393.
104. Ford, G.F.; Herman, P.S. Relative stabilities of nitrenium ions derived from polycyclic aromatic amines. Relationship to mutagenicity. Chem.-Biol. Interact., 1992, 81, 1-18.
105. Ford, G.F.; Griffin, G.R. Relative stabilities of nitrenium ions derived from heterocyclic amine food carcinogens: Relationship to mutagenicity. Chem.-Biol. Interact., 1992, 81, 19-33.
106. Sabbioni, G.; Wild, D. Quantitative structure-activity relationships of mutagenic aromatic and heteroaromatic azides and amines. Carcinogenesis, 1992, 13, 709-713.
107. Novak, M.; Rajagopal, S. Correlations of nitrenium ion selectivities with quantitative mutagenicity and carcinogenicity of the corresponding amines. Chem. Res. Toxicol., 2002, 15, 1495-1503 and references therein.
108. Knize, M.G.; Hatch, F.T.; Tanga, M.J.; Lau, E.Y.; Colvin, M.E. A QSAR for the mutagenic potencies of twelve 2-aminotrimethylimidazopyridine isomers: Structural, quantum chemical, and hydropathic factors. Environ. Mol. Mutagen., 2006, 47, 132-146.
109. Hatch, F.T.; Colvin, M.E.; Seidl, E.T. Structural and quantum chemical factors affecting mutagenic potency of aminoimidazoazaarenes. Environ. Mol. Mutagen., 1996, 27, 314-330.
110. Hatch, F.T.; Colvin, M.E. Quantitative structure-activity (QSAR) relationships of mutagenic aromatic and heterocyclic amines. Mutat. Res., 1997, 376, 87-96.
111. Hatch, F.T.; Knize, M.G.; Colvin, M.E. Extended quantitative structure-activity relationships for 80 aromatic and heterocyclic amines: Structural, electronic, and hydropathic factors affecting mutagenic potency. Environ. Mol. Mutagen., 2001, 38, 268-291.
112. Borosky, G.L. Ultimate carcinogenic metabolites from aromatic and heterocyclic aromatic amines: A computational study in relation to their mutagenic potency. Chem. Res. Toxicol., 2007, 20, 171-180.
113. Borosky, G.L. Carcinogenic carbocyclic and heterocyclic aromatic amines: a DFT study concerning their mutagenic potency. J. Mol. Graph. Model., in press.
114. Utesch, D.; Glatt, H.; Oesch, F. 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., 1987, 47, 1509-1515 and references therein.