Background: Large numbers of chemicals (natural and synthetic, including human dietary food components) are tested each year worldwide for potential genotoxic properties to protect humans and the environment against the consequences of exposure to such chemicals (cancer, infertility, accelerated ageing, and instability of ecosystems). For primary screening, fast in vitro and in vivo tests are used, but their predictive value is limited to the fact that they reflect the metabolism in humans inadequately. A methodological basis for improved tests by the use of human HepG2 cell system was developed. HepG2 cells were used as metabolic activation system as well as target for evaluating DNA damage. HepG2 cells are proven to have the same Phase I and II enzymatic profiles as human hepatocytes. Objectives: To apply this cell system and series of updated biological assays such as chromosomal alteration, as well as state of the art genomic and proteomic assays to investigate and characterize a broad variety of compounds to which humans are exposed via diet or the environment, including polycyclic aromatic hydrocarbons, heterocyclic aromatic amines and acrylamide, nitrosamines, heavy metals, pesticides, plant constituents, mycotoxins, complex foods (beverages, plant juices), environmental mixtures (air and water), cytostatic drugs and nitrosamines. Methods: The method is illustrated in Figure 1. Results: The results can provide information on initial DNA damage, repair kinetic, biological consequences, gene- protein- and enzymatic-expression profiles. These outcomes are required to develop measures to protect humans against exposure to dietary and environmental genotoxins. Conclusion: The characterization of different classes of chemicals will contribute substantially to the assessment of their health risks for humans. The outcomes may also reveal the potential of specific dietary components that can serve as co- and anti-carcinogens. Furthermore, the potential of HepG2 cell system as an alternative to use of vertebrate animals in genotoxicity testing can be evaluated.


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