Abstract
Biotransformation is a complex enzyme system required in the metabolic activation of xenbobiotics, in which hydrophobic compounds are converted into hydrophilic ones which then may be excreted. The liver is the major organ for the metabolism of xenobiotics; however, other organs, e.g., lung, intestine, skin and brain, may participate in biotransformation as well. Metabolic activation is an essential prerequisite for many chemicals before they can be excreted. The formation of a reactive intermediate is the critical step in biotransformation. This intermediate is of toxicological relevance, as it can distort the physiological functions of a cell by reacting with DNA, RNA or protein, leading to cell death or malignant transformation of a cell into a cancer cell. The key enzymes in biotransformation are the monooxygenases cytochrome P450s, which transfer an atomic oxygen thereby activating a chemical in several ways. Although these cytochrome P450s are not substrate specific in a strict sense, there are preferences, e.g., cytochrome P450 1A1 for polycyclic aromatic hydrocarbons such as benzo[a]pyrene, or 1A2 for aromatic amines. For risk assessment, it is of fundamental interest to know which enzymes are involved and which metabolites are formed, as well as to understand the mechanism by which these metabolites became toxic to a cell.
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References
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© 1998 Springer-Verlag Berlin Heidelberg
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Doehmer, J. (1998). Current Status of Genetically Engineered In Vitro Systems for Biotransformation. In: Clynes, M. (eds) Animal Cell Culture Techniques. Springer Lab Manual. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80412-0_24
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DOI: https://doi.org/10.1007/978-3-642-80412-0_24
Publisher Name: Springer, Berlin, Heidelberg
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