Most environmental mutagens and carcinogens require metabolic activation to electro- philic intermediates capable of reacting with cellular target structures, such as DNA. These electrophilic intermediates are in addition subject to metabolic detoxification. This metabolism is mainly controlled by enzymes whose expression is very variable. Among other things, various enzymes are inducible by environmental chemicals. Understanding the toxicology of chemicals (for example, species differences, idiosyncrasias, organotropisms) therefore requires knowledge of critical host factors. One approach towards this goal involves the use of purified enzymes in metabolism and toxicological studies (Glatt et al., 1983; Glatt and Oesch, 1986). This approach, however, is laborious, the purification may alter enzymatic properties, and it may be difficult to rule out the influence of impurities in the enzyme preparation, especially when large families of structurally closely related enzymes exist, as is common in xenobiotic metabolism.
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- Stable Expression of Heterologous Microsomal Epoxide Hydrolase in BHK21 Cells: Influence on the Mutagenicity of Benzo[a]pyrene 4,5-Oxide
H. R. Glatt
- Springer Berlin Heidelberg