Xenobiotic metabolism: a view through the metabolometer

Patterson, Andrew D; Gonzalez, Frank J; Idle, Jeffrey R (2010). Xenobiotic metabolism: a view through the metabolometer. Chemical research in toxicology, 23(5), pp. 851-60. Washington, D.C.: American Chemical Society 10.1021/tx100020p

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The combination of advanced ultraperformance liquid chromatography coupled with mass spectrometry, chemometrics, and genetically modified mice provide an attractive raft of technologies with which to examine the metabolism of xenobiotics. Here, a reexamination of the metabolism of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), the suspect carcinogen areca alkaloids (arecoline, arecaidine, and arecoline 1-oxide), the hormone supplement melatonin, and the metabolism of the experimental cancer therapeutic agent aminoflavone is presented. In all cases, the metabolic maps of the xenobiotics were considerably enlarged, providing new insights into their toxicology. The inclusion of transgenic mice permitted unequivocal attribution of individual and often novel metabolic pathways to particular enzymes. Last, a future perspective for xenobiotic metabolomics is discussed and its impact on the metabolome is described. The studies reviewed here are not specific to the mouse and can be adapted to study xenobiotic metabolism in any animal species, including humans. The view through the metabolometer is unique and visualizes a metabolic space that contains both established and unknown metabolites of a xenobiotic, thereby enhancing knowledge of their modes of toxic action.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology

UniBE Contributor:

Idle, Jeffrey

ISSN:

0893-228X

Publisher:

American Chemical Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:11

Last Modified:

04 May 2014 23:05

Publisher DOI:

10.1021/tx100020p

PubMed ID:

20232918

Web of Science ID:

000277597400005

URI:

https://boris.unibe.ch/id/eprint/1735 (FactScience: 203675)

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