Most environmental carcinogens require metabolic activation to reactive intermediates and are mutagenic in appropriate test systems. During the last decade, the cDNAs of numerous xenobiotic-metabolizing enzymes have been cloned. The individually expressed enzymes were used to study their substrate specificities and their inhibition by other compounds. Various enzymes were expressed directly in target cells of in vitro mutagenicity tests. This is illustrated in the present study for rat and human sulphotransferases (SULTs) expressed in Salmonella typhimurium TA1538. Numerous compounds were mutagenic in the new test system. Some of these promutagens were activated by several different SULT forms, whereas many other promutagens were activated with high selectivity by a specific enzyme form, but not by genetically closely related forms from the same species (e.g. allelic variants) or orthologous enzymes from other species. Similar findings have been made using recombinant test systems for specific forms of other classes of enzymes (e.g. cytochromes P450). This high selectivity in activation (and inactivation) may explain some organotropisms as well as species and inter-individual differences in the action of carcinogens. Many carcinogen-metabolizing enzymes are induced or inhibited by other xenobiotics. Such interactions can be exploited for chemo-prevention, which however may be carcinogen-and tissue-dependent.
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Conference Article|
February 01 2000
An overview of bioactivation of chemical carcinogens
H. R. Glatt
H. R. Glatt
1German Institute of Human Nutrition (DlfE), Arthur-Scheunert-Allee 114-116, 14458 Potsdam-Rehbruecke, Germany
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Publisher: Portland Press Ltd
Received:
August 06 1999
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2000 Biochemical Society
2000
Biochem Soc Trans (2000) 28 (2): 1–6.
Article history
Received:
August 06 1999
Citation
H. R. Glatt; An overview of bioactivation of chemical carcinogens. Biochem Soc Trans 1 February 2000; 28 (2): 1–6. doi: https://doi.org/10.1042/bst0280001
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