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Cytotoxicity, DNA Fragmentation, and DNA Repair Synthesis in Primary Human Hepatocytes

  • Giovanni Brambilla
  • Antonietta Martelli
Part of the Methods in Molecular Biology™ book series (MIMB, volume 43)

Abstract

The well-documented existence of interspecies differences in the responses elicited by exposure to chemical agents (1, 2, 3) represents the main difficulty in the extrapolation to humans of the results of toxicity studies carried out in laboratory animals or in in vitro systems employing as targets prokaryotes, lower eukaryotes, or mammalian cells. Growing evidence indicates that the most important cause of these species-related differences is the different handling of xenobiotics by metabolic activation/detoxification processes. Primary cultures of human hepatocytes that can be prepared from material discarded during the course of prescribed surgery offer the unique advantage of directly assessing the cytotoxic and genotoxic effects of chemicals in cells of our species possessing a comprehensive metabolic capability.

Keywords

Human Hepatocyte Disodium EDTA Trypan Blue Solution Heating Water Bath Tetraethylammonium Hydroxide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Langenbach, R., Nesnow, S., and Rice, J. M. (1983) Organ and Species Specificity in Chemical Carcinogenesis Plenum, New York.Google Scholar
  2. 2.
    Hsu, L., Harris,, Lipsky, M. M, Snyder, S, and Trump, F. (1987) Cell and species differences in metabolic activation of chemical carcinogens. Mutat. Res. 177, 1–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Phillipson, C. E. and Ioannides, C. (1984) A comparative study of the bioactivation of nitrosamines to mutagens by various animal species including man Carcinogenesis 5, 1091–1094PubMedCrossRefGoogle Scholar
  4. 4.
    Strom, S., Jirtle, R. L, Jones, R. S., Novicki, D L, Rosenberg, M. R, Novotny, A., Irons, G., McLain, J. R., and Michalopoulos, G. (1982) Isolation, culture, and transplantation of human hepatocytes. J. Natl. Cancer Inst. 68, 771–778PubMedGoogle Scholar
  5. 5.
    Maekubo, H., Ozaki, S., Mitmaker, S., and Kalant, N (1982) Preparation of human hepatocytes from primary culture In Vitro 18, 483–491.PubMedCrossRefGoogle Scholar
  6. 6.
    Butterworth, E., Bermudez, E, Smith-Oliver, T, Earle, L, Cattley, R, Martin, J., Popp, J. A, Strom, S, Jirtle, R., and Michalopoulos, G. (1984) Lack of genotoxic activity of di(2-ethylhexyl) phthalate (DEHP) in rat and human hepatocytes. Carcinogenesis 5, 1329–1335PubMedCrossRefGoogle Scholar
  7. 7.
    Robbiano, L., Gazzaniga, G. M., Martelli, A., Pino, A, and Brambilla, G. (1986) DNA-damaging activity of tripelennamine in primary cultures of human hepatocytes. Mutat. Res. 173, 229–232.PubMedCrossRefGoogle Scholar
  8. 8.
    Martelli, A., Robbiano, L., Ghia, M., Giuliano, L., Angelini, G., and Brambilla, G. (1986) A study of the potential genotoxicity of cimetidine using human hepatocyte primary cultures; discrepancy from results obtained in rat hepatocytes. Cancer Lett 30, 11–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Martelli, A., Robbiano, L., Gazzaniga, G M., and Brambilla, G (1988) Comparative study of DNA damage and repair induced by ten N-nitroso compounds in primary cultures of human and rat hepatocytes. Cancer Res. 48, 4144–4152.PubMedGoogle Scholar
  10. 10.
    Butterworth, E, Smith-Oliver, T, Earle, L, Loury, D J, White, R D, Doolittle, D. J., Working, P K., Cattley, R, Jirtle, R., Michalopoulos, G., and Strom, S. (1989) Use of primary cultures of human hepatocytes in toxicology studies. Cancer Res 49, 1075–1084PubMedGoogle Scholar
  11. 11.
    Robbiano, L., Martelli, A., Allavena, A., Mazzei, M., Gazzaniga, G. M., and Brambilla, G. (1991) Formation of the N-nitroso derivatives of six β-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytes Cancel Res. 51, 2273–2279.Google Scholar
  12. 12.
    Cesarone, F., Bolognesi, C., and Santi, L. (1979) Improved microfluorometric DNA determination in biological material using 33258 Hoechst. Anal. Biochem 100, 188–197.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc , Totowa, NJ 1995

Authors and Affiliations

  • Giovanni Brambilla
    • 1
  • Antonietta Martelli
    • 1
  1. 1.Department of PharmacologyUniversity of GenoaItaly

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