Identification of the structural requirements for mutagenicity by incorporating molecular flexibility and metabolic activation of chemicals I: TA100 model

Chemical Research in Toxicology

Volumn 17, Issue 6, 2004, Pages 753-766

  Mekenyan, Ovanes ^a   Dimitrov, Sabcho ^a   Serafimova, Rossitsa ^a   Thompson, Ed ^b   Kotov, Stefan ^a   Dimitrova, Nadezhda ^a   Walker, John D ^c  

^a ASSEN ZLATAROV UNIVERSITY   (Bulgaria)

^b PROCTER AND GAMBLE COMPANY   (United States)

^c U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 AMINO 2 CARBOXYLATE 4 NITROANTHRAQUINONE; 1,3 DINITROBENZENE; 2 ISOPROPYL 4 PHENYLNITROBENZENE; 2 METHYL 7 NITRO 9H FLUORENE; 2 NAPHTHYLAMINE; 2 NITROFLUORENE; 2 NITRONAPHTHALENE; 3 (1,1 DIMETHYLETHYL) 4 NITRO 1,1' BIPHENYL; 3 (1,1 DIMETHYLETHYL) 4 NITROSO 1,1' BIPHENYL; 3 METHYL 4 NITROBIPHENYL; 3,5 DIETHYL 4 NITRO 1,1' BIPHENYL; 3,5 DINITROANILINE; 4 (1,1 DIMETHYLETHYL) 4' NITRO 1,1' BIPHENYL; 4 ETHYL 3 NITROBIPHENYL; 4 ETHYL 4' NITRO 1,1' BIPHENYL; 4 METHYL 4' NITROBIPHENYL; 4 METHYL 4' NITROSTILBENE; 4 NITROSOBIPHENYL; 9 METHYL 2 NITROCARBAZOLE; BIPHENYL DERIVATIVE; DIAZOLIDINYL UREA; FLUORENE DERIVATIVE; LIVER ENZYME; MUTAGENIC AGENT; N HYDROXY 2 NAPHTHYLAMINE; N HYDROXY 4 BIPHENYLAMINE; NICOTINE; NITROBENZENE DERIVATIVE; STILBENE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AMES TEST; ARTICLE; BACTERIAL STRAIN; CHEMICAL STRUCTURE; COMPUTER SYSTEM; CONTROLLED STUDY; DATA BASE; DECISION THEORY; GENOTOXICITY; METABOLIC ACTIVATION; MUTAGENICITY; NONHUMAN; PREDICTION; PROBABILITY; QUANTITATIVE STRUCTURE ACTIVITY RELATION; VALIDATION PROCESS;

BIOTRANSFORMATION; COMPUTER SIMULATION; DECISION TREES; MUTAGENESIS; MUTAGENICITY TESTS; MUTAGENS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; SALMONELLA TYPHIMURIUM;

BACTERIA (MICROORGANISMS);

EID: 3042807182     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx030049t     Document Type: Article

References (58)

1. Ames, B. N., McCann, J., and Yamasaki, E. (1975) Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat. Res. 31, 347-364.
2. Maron, D. M., and Ames, B. N. (1983) Revised method for the Salmonella mutagenicity test. Mutat. Res. 3113, 173-215.
3. Compadre, R. L., Debnath, A. K., Shusterman, A. J., and Hansch, C. (1990) LUMO energies and hydrophobicity as determinants of mutagenicity by nitroaromatic compounds in Salmonella typhimurium. Environ. Mol. Mutagen. 15, 44-55.
4. Debnath, A. K., Compadre, R. L., Shusterman, A. J., and Hansch, C. (1992) Quantitative structure-activity relationship investigation of role of hydrophobicity in regulating mutagenicity in the Ames test: 2. Mutagenicity of aromatic and heteroaromatic nitro compounds in Salmonella typhimurium TA100. Environ. Mol. Mutagen. 19, 53-70.
5. Debnath, A. K., Shusterman, A. J., and Hansch, C. (1992) Quantitative Structure-activity relationship investigation of role of hydrophobicity in regulating mutagenicity in the Ames test: 1. Mutagenicity of aromatic and heteroaromatic amines Salmonella typhimurium TA98 and TA100. Environ. Mol. Mutagen. 19, 37-52.
6. Smith, C. J., Hansch, C., and Mortan, M. J. (1997), QSAR treatment of multiple toxicities: the mutagenicity and citotoxicity of quinolines. Mutat. Res. 379, 167-175.
7. Chung, K. T., Chen, S. C., Wong, T. Y., Li, Y. S., Wei, C. I., and Chou, M. W. (2000) Mutagenicity studies of benzidine and its analogues: structure-activity relationships. Toxicol. Sci. 56, 351-356.
8. Tuppurainen, K. (1994) QSAR approach to molecular mutagenicity. A survey and a case study: mx compounds. J. Mol. Struct. 306, 49-56.
9. Shusterman, A. J., Debnath, A. K., Hansch, C., Horn, G. W., Fronczek, F. R., Greene, A. C., and Watkins, S. F. (1989) Mutagenicity of dimethyl heteroaromatic triazenes in the Ames test: The role of hydrophobicity and electronic effect. Mol. Pharmacol. 36, 939-944.
10. Benigni, R., and Giuliani, A. (1996) Quantitative structure-activity relationship (QSAR) studies of mutagens and carcinogense. Med. Res. Rev. 16 (3), 267-284.
11. Sanderson, D. M, and Earnshaw, C. G. (1991) Computer prediction of possible toxic action from chemical structure: the DEREK system. Hum. Exp. Toxicol. 10, 261-273.
12. Smithing, M. P, and Darvas, F. (1992) HazardExpert: An expert system for predicting chemical toxicity. In SF Finlay (Robinson, S. F., and Armstrong, D. J., Eds.) pp 191-200, Food Safety Assessment, American Chemical Society, Washington.
13. Woo, Y.-T., Lai, D., Argus M., and Arcos, J. (1995) Development of structure activity relationship rules for predicting carcinogenic potential of chemicals. Toxicol. Lett. 79, 219-228.
14. Ashby, J. (1985) Fundamental structural alerts to potential carcinogenicity or noncarcinogenicity. Environ. Mutagen. 7, 919-921.
15. Ashby, J., and Tennant, R. W. (1988) Chemical structure. Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested by the U.S. NTP. Mutat. Res. 204, 17-115.
16. Ashby, J., and Tennant, F. W. (1991) Definitive relationships among chemicals structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat. Res. 257, 229-306.
17. Ashby, J., and Paton, D. (1993) The influence of chemicals structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 55 different human carcinogen exposures. Mutat. Res. 286, 3-74.
18. Richard, A. M. (1994) Application of SAR methods to noncongeneric databases associated with carcinogenicity and mutagenicity: Issues and approaches. Mutat. Res. 305, 73-97.
19. Enslein, K. (1988) Something is wrong with this title? An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol. Ind. Health 4, 479-498.
20. Klopman, G. (1992) MultiCASE 1. A hierarchical computer automated structure evaluation program. Quant. Struct.-Act. Relat. 11, 176-184.
21. King, R. D., and Srinivasan, A. (1996) Prediction of rodent carcinogenicity bioassays from molecular structure using inductive logic programming. Environ. Health Perspect. 104 (S5), 1031-1040.
22. Schultz, T. W., Cronin, M. T. D., and Netzeva, T. I. (2003) The present status of QSAR in toxicology. J. Mol. Struct. (THEOCHEM) 622, 23-38.
23. Purdy, R. (1996) A mechanism-mediated model for carcinogenicity: Model content and prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 25 organic chemicals. Environ. Health Perspect. 104, 1085-1094.
24. Lewis, D. F. V., Ioannides, C., and Parke, D. V. (1993) Validation of a novel molecular orbital approach (COMPACT) for the prospective safety evaluation of chemicals, by comparison with rodent carcinogenicity and Salmonella mutagenicity data evaluated by the US NCI/NTP. Mutat. Res. 291, 61-77.
25. Mekenyan, O. G., Ivanov, J. M., Karabunarliev, S. H., Bradbury, S. P., Ankley, G. T., and Karcher, W. (1997) A computationally based hazard identification algorithm that incorporates ligand flexibility. 1. Identification of potential androgen receptor ligands. Environ. Sci. Technol. 31, 3702-3711.
26. Mekenyan, O. G., Nikolova, N., Schmieder, P., and Veith, G. D. (2004) COREPA-M: A Multi-dimensional formulation of COREPA. QSAR Comb. Sci. 23, 5-18.
27. Mekenyan, O. G., Nikolova, N., Karabunarliev, S., Bradbury, S., Ankley, G., and Hansen, B. (1999) New developments in a hazard identification algorithm for hormone receptor ligands. Quant. Struct.-Act. Relat. 18, 139-153.
28. Bradbury, S. P., Mekenyan, O. G., Kamenska, V. B., Schmieder, P., and Ankley, G. T. (2000) A computationally-based identification algorithm for estrogen receptor ligands. Part I. Predicting hER binding affinity. Toxicol. Sci. 58, 253-269.
29. Jaworska, J., Dimitrov, S., Nikolova, N., and Mekenyan, O. (2001) Probabilistic assessment of biodegradability based on metabolic pathways: CATABOL system. SAR QSAR Environ. Res. 13, 307-323.
30. Dimitrov, S., Breton, R., MacDonald, D., Walker, J. D., and Mekenyan, O. (2001) Quantitative prediction of biodegradability, metabolite distribution and toxicity of stable metabolites. SAR QSAR Environ. Res. 13, 445-455.
31. Dimitrov, S. D., Dimitrova, N. C., Walker, J. D., Veith, G. D., and Mekenyan, O. G. (2003) Bioconcentration potential predictions based on molecular attributes - an early warning approach for chemicals found in humans, birds, fish and wildlife. QSAR Comb. Sci. 22, 58-68.
32. Snyder, R. T., Chepiga, T., Yang, C. S., Tomas, H., Platt, K., and Oesch, F. (1993) Benzene metabolism by reconstituted cytochromes P450 2B1 and 2E1 and its modulation by cytochrome b5 microsomal epoxide hydrolase and glutathione transferases: Evidence for an important role of microsomal epoxide hydrolase in the formation of hydroquinone. Toxicol. Appl. Pharmacol. 122, 172-181.
33. Liehr, J. G., Somasunderam, I. A., and Roy, D. (1998) Natural and anthropogenic environmental oestrogens: The scientific basis for risk assessment. Metabolism and fate of xeno-oestrogens in man. Pure Appl. Chem. 70 (9), 1747-1758.
34. Scapellato, M. L., Marcuzzo, G., Mastrangelo, G., Sessa, G., Cellini, M., De Rosa, E., Saia, B., and Bartolucci, G. B. (1998) Environmental and biological monitoring of styrene exposure: Urinary excretion of D-glucaric acid compared with exposure indices. J. Occup. Health 40, 313-318.
35. Park, B. K., Kitteringham, N. R., and O'Neill, P. M. (2001) Metabolism of fluorine-containing drugs. Annu. Rev. Pharmacol. Toxicol. 41, 443-470.
36. 14C-tazadolene succinate in the dog. Xenobiotica 22, 963.
37. den Besten, C., Bennik, M. M., Van Tersel, M., Peters, M. A. W., Teunis, C., and van Bladeren, P. J. (1994) Comparison of the urinary metabolite profiles of hexachlorobenzene and pentachlorobenzene in the rat. Chem.-Biol. Interact. 90, 121-137.
38. Tai, H. L., McReynolds, J. J., Goldstein, J. A., Eugster, H. P., Sengstag, C., Alworth, W. L., and Olson, J. R. (1993) Cytochrome P4501A1 mediates the metabolism of 2,3,7,8-tetrachlorodibenzofuran in the rat and human. Toxicol. Appl. Pharmacol. 123, 34-42.
39. Nakajama, M., Iwata, K., Yamamoto, T., Funae, Y., Yoshida, T., and Kurowa, Y. (1998) Nicotine metabolism in liver microsomes from rats with acute hepatitis or cirrhosis. Drug Metab. Dispos. 26 (1), 36.
40. Buckpitt, A. R., Castagnoli, N., Jr., Nelson, S. D., Jones, A. D., and Bahnson, L. S. (1987) Stereoselectivity of naphthalene epoxidation by mouse, rat and hamster pulmonary, hepatic and renal microsomal enzymes. Drug Metab. Dispos. 15, 491.
41. Corbett, M. D., and Corbett, B. R. (1985) Enzymatic N-oxidation of 4-nitroaniline. Biochem. Arch. 1, 115-120.
42. Nystrom, D. D., and Rickert, D. E. (1987) Metabolism and excretion of dinitrobenzenes by male Fischer-344 rats. Drug Metab. Dispos. 15, 821-825.
43. Kedderis, G. L., Summer, S. C. J., Held, S. D., Batra, R., Turner, M. J., Robert, E., and Fennel, T. R. (1993) Dose-dependent urinary excretion of acrylonitrile metabolites by rats and mice. Toxicol. Appl. Pharmacol. 120, 288-287.
44. Peterson, F. J., and Holtzman, J. Z. (1980) Drug metabolism in the liver. A perspective. In Extrahepatic Metabolism of Drugs and Other Foreign Compounds (Gran, T. E., Ed.) pp 1-121, MTP-Press Ltd., Lancaster, England.
45. Sabourin, P. J., Burka, L. T., Bechtold, W. E., Dahl, A. R., Hoover, M. D., Chang, L. Y., and Henderson, R. F. (1992) Species differences in urinary butadiene metabolites; identification of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane, a novel metabolite of butadiene. Carcinogenesis 13, 1633-1638.
46. Mekenyan, O. G., Dimitrov, D., Nikolova, N., and Karabunarliev, S. (1999b) Conformational coverage by a genetic algorithm. Chem. Inf. Comput. Sci. 39/6, 997-1016.
47. Stewart, J. J. P. (1990) MOPAC: A semiempirical molecular orbital program. J. Comput.-Aided Mol. Des. 4, 1-105.
48. Stewart, J. J. P. (1993) MOPAC 93, Fujitsu Limited, 9-3, Nakase 1-Chome, Mihama-ku, Chiba-city, Chiba 261, Japan, and Stewart Computational Chemistry, 15210 Paddington Circle, Colorado Springs, CO 80921.
49. Ivanov, J. M., Mekenyan, O. G., Bradbury S. P., and Schuurmann, G. (1998) A kinetic analysis of the conformational flexibility of steroids. Quant. Struct.-Act. Relat. 17, 437-449.
50. Bradbury, S. P., Mekenyan, O. G., and Ankley, G. T. (1998) The role of ligand flexibility in predicting biological activity: Structure-activity relationships for aryl hydrocarbon, estrogen and androgen receptor binding affinity. Environ. Toxicol. Chem. 17, 15-25.
51. Mekenyan, O. G., Kamenska, V., Schmieder, P., Ankley, G., and Bradbury, S. (2000) A computationally-based identification algorithm for estrogen receptor ligands. Part II. Evaluation of a hER binding affinity model. Toxicol. Sci. 58, 270-281.
52. Mekenyan, O. (2002) Dynamic QSAR techniques: Application in drug design and toxicology. Curr. Pharm. Des. 8, 1605-1621.
53. CEFIC (European Chemical Industry Council). (2002) Report from the workshop on regulatory acceptance of QSARs for human health and environmental endpoints, pp 58, Setubal, Portugal, March 4-6, 2002, report available from rbu@cefic.be.
54. Meylan, W. M., and Howard, P. H. (1995) Atom/fragment contribution method for estimating octanol-water partition coefficients. J. Pharm. Sci. 84, 84-92.
55. Wackett, L. P., and Hershberger, C. D. (2001) Biocatalysis and biodegradation: microbial transformation of organic compounds, ASM Press, Washington, DC.
56. Yeruhshalomy, J. (1947) Statistical problems in assessing methods of medical diagnosis, with special reference to X-ray techniques. Public Health Rep. 62, 1432-1449.
57. Byrd, G. D., Davis, R. A., and Kazemi, V. E. (1995) Comparison of methods for determining nicotine and its metabolites in urine. Conference of the Society for Research on Nicotine and Tobacco, poster no. 9, San Diego, CA, 24-25 March.
58. Tricker, A. R. (2003) Nicotine metabolism, human drug metabolism polymorphisms, and smoking behaviour. Toxicology 183, 151-173.