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Efficiency of evaluating the carcinogenicity of chemical substances in short-term tests and the SAR model

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Abstract

The efficiency of estimating the carcinogenic activity of chemical substances was compared for five short-term tests and structure-activity relationships (SAR) analysis. The set included 84 substances with known biological testing results obtained by the Ames test, bacterial SOS chromotest (SOS), chromosome aberration (CA) cytogenetic test, sister chromatid exchange (SHE) test, and gene mutation (GM) test with mammalian cells in vitro and by carcinogenicity assays in rodents in vivo. Structural descriptors were selected using an original database, which included the structural formulas of substances with known carcinogenic activity in rodents. Original software was created to generate and select the descriptors that statistically coincided with carcinogenic activity. The descriptors that were associated exclusively with carcinogenic substances from the database and the tests that produced positive results exclusively with carcinogens were used to evaluate the carcinogenic activity of the substances. A combination of three short-term tests (Ames, SOS, and CA tests) and the SAR model proved to identify carcinogenicity for more than 60% of carcinogens.

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References

  1. Tennant, R.W., Margolin, B.H., Shelby, M.D., et al., Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays, Science, 1987, vol. 236, pp. 933–941.

    Article  CAS  PubMed  Google Scholar 

  2. Zeiger, E., Haseman, J.K., Shelby, M.D., et al., Evaluation of Four in vitro Genetic Toxicity Tests for Predicting Rodent Carcinogenicity: Confirmation of Earlier Results with 41 Additional Chemicals, Environ. Mol. Mutagen., 1990, vol. 18, pp. 1–14.

    Article  Google Scholar 

  3. Haseman, J.K. and Clark, A.M., Carcinogenicity Results for 114 Laboratory Animal Studies Used to Assess the Predictivity of Four in vitro Genetic Toxicity Assays for Rodent Carcinogenicity, Environ. Mol. Mutagen., 1990, vol. 18, pp. 15–31.

    Article  Google Scholar 

  4. Quillardet, P. and Hofnung, M., The SOS Chromotest, a Colorimetric Bacterial Assay for Genotoxins: Procedures, Mutat. Res., 1985, vol. 147, pp. 65–78.

    CAS  PubMed  Google Scholar 

  5. Oda, Y., Nakamura, S., Oki, I., et al., Evaluation of a New System (umu-Test) for the Detection of Environmental Mutagens and Carcinogens, Mutat. Res., 1985, vol. 147, pp. 219–229.

    CAS  PubMed  Google Scholar 

  6. Dzhedzhelava, D.A., Egorov, I.A., and Tarasov, V.A., Induction of SOS Function in Escherichia coli after Exposure to Various Types of Chemical Mutagens, Russ. J. Genet., 1989, vol. 25, no. 9, pp. 1551–1558.

    CAS  Google Scholar 

  7. Schultz, T.W., Cronin, M.T.D., and Netzeva, T.I., The Present Status of QSAR in Toxicology, J. Mol. Struct. (Theochem), 2003, vol. 622, pp. 23–28.

    Article  CAS  Google Scholar 

  8. Schultz, T.W., Cronin, M.T.D., Walker, J.D., and Aptula, A.O., Quantitative Structure-Activity Relation ships (QSARs) in Toxicology: A Historical Perspective, J. Mol. Struct. (Theochem), 2003, vol. 622, pp. 1–22.

    Article  CAS  Google Scholar 

  9. Dearden, J.C., In silico Prediction of Drug Toxicity, J. Computer-Aided Mol. Design, 2003, vol. 17, pp. 119–127.

    Article  CAS  Google Scholar 

  10. Benigni, R., The First US National Toxicology Program Exercise on the Prediction of Rodent Carcinogenicity: Definitive Results, Mutat. Res., 1997, vol. 387, p. 35–45.

    Article  PubMed  Google Scholar 

  11. Benigni, R. and Zito, R., The Second National Toxicology Program Comparative Exercise on the Prediction of Rodent Carcinogenicity: Definitive Results, Mutat. Res., 2004, vol. 566, pp. 49–63.

    Article  CAS  PubMed  Google Scholar 

  12. http://ntp.niehs.nih.gov

  13. http://toxnet.nlm. nih.gov

  14. Yasunaga, K., Kiyonari, A., Oikawa, T., et al., Evaluation of the Salmonella umu Test with 83 NTP Chemicals, Environ. Mol. Mutagen., 2004, vol. 44, pp. 329–345.

    Article  CAS  PubMed  Google Scholar 

  15. Quillardet, P., Bellecombe, C., and Hofnung, M., The SOS Chromotest, a Colorimetric Bacterial Assay for Genotoxins: Validation Study with 83 Compounds, Mutat. Res., 1985, vol. 147, pp. 79–95.

    CAS  PubMed  Google Scholar 

  16. Ashby, J., Tennant, R.W., Zeiger, E., and Stasiewicz, S., Classification According to Chemical Structure, Mutagenicity to Salmonella and Level of Carcinogenicity of a Further 42 Chemicals Tested for Carcinogenicity by the US National Toxicology Program, Mutat. Res., 1989, vol. 223, pp. 73–103.

    Article  CAS  PubMed  Google Scholar 

  17. Reifferscheid, G. and Heil, J., Validation of the SOS/umu Test Results of 486 Chemicals and Comparison with the Ames Test and Carcinogenicity Data, Mutat. Res., 1996, vol. 369, pp. 129–145.

    Article  CAS  PubMed  Google Scholar 

  18. http://potency.berkeley.edu/cpdb.html

  19. http://chemfinder.cambridgesoft.com

  20. Hudson, D.J., Statistics for Physicists, Geneva: CERN, 1967.

    Google Scholar 

  21. Tarasov, V.A., Principles of Qualitative and Quantitative Genetic Hazard Assessment of Chemical Substances, in Mutageny i kantserogeny okruzhayushchei sredy i nasledstvennost’ cheloveka (Environmental Mutagens and Carcinogens and the Human Heredity), Moscow, 1994, pp. 3–66.

  22. Rozenblit, A.B. and Golender, V.E., Logic Combinatory Methods of Drug Design, Riga: Zinatne, 1983.

    Google Scholar 

  23. Ames, B.N. and Gold, L.S., Chemical Carcinogenesis: Too Many Rodent Carcinogens, Proc. Natl. Acad. Sci. USA, 1990, vol. 87, pp. 7772–7776.

    Article  CAS  PubMed  Google Scholar 

  24. Gold, L.S. and Zeiger, E., Handbook of Carcinogenic Potency and Genotoxicity Databases, Boca Raton: CRC, 1997.

    Google Scholar 

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Authors and Affiliations

  1. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117609, Russia

    V. A. Tarasov, N. A. Tsarenko, V. A. Melnik, O. N. Mustafaev, G. P. Makedonov & A. V. Tarasov

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  1. V. A. Tarasov
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  2. N. A. Tsarenko
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  3. V. A. Melnik
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  4. O. N. Mustafaev
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  5. G. P. Makedonov
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  6. A. V. Tarasov
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Correspondence to N. A. Tsarenko.

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Original Russian Text © V.A. Tarasov, N.A. Tsarenko, V.A. Melnik, O.N. Mustafaev, G.P. Makedonov, A.V. Tarasov, 2009, published in Genetika, 2009, Vol. 45, No. 12, pp. 1674–1684.

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Tarasov, V.A., Tsarenko, N.A., Melnik, V.A. et al. Efficiency of evaluating the carcinogenicity of chemical substances in short-term tests and the SAR model. Russ J Genet 45, 1480–1489 (2009). https://doi.org/10.1134/S1022795409120126

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  • DOI: https://doi.org/10.1134/S1022795409120126

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