Possible role of the glucuronide conjugate in the biochemical mechanism op binding of the carcinogen N-hydroxy-2-acetylaminofluorene to rat-liver deoxyribonucleic acid in vivo

Irving, Charles C.; Veazey, Richard A.; Russell, Laretta T.

doi:10.1016/0009-2797(69)90016-7

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2012

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Cited by 24 publications

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Bioactivation by Phase‐II‐Enzyme‐Catalyzed Conjugation of Xenobiotics

Grillo

2012

Encyclopedia of Drug Metabolism and Interactions

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Phase‐II‐enzyme‐catalyzed conjugation of xenobiotics with endogenous cofactors leads to hydrophilic derivatives that, in most cases, functions in the elimination and detoxification of xenobiotics from the body. However, this process can also mediate their bioactivation to chemically‐reactive and hence potentially toxic metabolites. The major conjugation reactions known to be involved in xenobiotic bioactivation are glucuronidation, sulfonation, acetylation, GSH conjugation, and acyl‐S‐CoA formation. Chemically‐reactive metabolites of xenobiotics can lead to covalent binding to protein and/or nucleic acids which some cases leads to intrinsic and/or idiosyncratic toxicity and carcinogenicity. This chapter will cover the known mechanisms of xenobiotic bioactivation by phase‐II‐drug‐conjugating enzymes.

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