Abstract
The well-documented existence of interspecies differences in the responses elicited by exposure to chemical agents (1–3) 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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Langenbach, R., Nesnow, S., and Rice, J. M. (1983) Organ and Species Specificity in Chemical Carcinogenesis Plenum, New York.
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.
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, 1091–1094
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, 771–778
Maekubo, H., Ozaki, S., Mitmaker, S., and Kalant, N (1982) Preparation of human hepatocytes from primary culture In Vitro 18, 483–491.
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, 1329–1335
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.
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.
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.
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, 1075–1084
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.
Cesarone, F., Bolognesi, C., and Santi, L. (1979) Improved microfluorometric DNA determination in biological material using 33258 Hoechst. Anal. Biochem 100, 188–197.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Humana Press Inc , Totowa, NJ
About this protocol
Cite this protocol
Brambilla, G., Martelli, A. (1995). Cytotoxicity, DNA Fragmentation, and DNA Repair Synthesis in Primary Human Hepatocytes. In: O’Hare, S., Atterwill, C.K. (eds) In Vitro Toxicity Testing Protocols. Methods in Molecular Biology™, vol 43. Humana Press. https://doi.org/10.1385/0-89603-282-5:59
Download citation
DOI: https://doi.org/10.1385/0-89603-282-5:59
Publisher Name: Humana Press
Print ISBN: 978-0-89603-282-8
Online ISBN: 978-1-59259-530-3
eBook Packages: Springer Protocols