UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues

Nathan R Jones; Philip Lazarus

doi:10.1124/dmd.113.054718

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UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues

Journal article

Open access

Peer reviewed

UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues

Nathan R Jones and Philip Lazarus

Drug metabolism and disposition, Vol.42(4), pp.529-536

04/2014

DOI: https://doi.org/10.1124/dmd.113.054718

Handle:

https://hdl.handle.net/2376/109088

PMCID: PMC3965906

PMID: 24459179

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Abstract

Gene Expression Regulation, Enzymologic

Glucuronosyltransferase - genetics

Limit of Detection

Tobacco - metabolism

Humans

Carcinogens - pharmacokinetics

Gene Expression Profiling

Organ Specificity

Tobacco - toxicity

The UDP-glucuronosyltransferase (UGT) 2B subfamily of enzymes plays an important role in the metabolism of numerous endogenous and exogenous compounds, including various carcinogens present in tobacco smoke. The goal of the present study was to examine the levels of expression of individual UGT2B genes in various tissues that are targets for tobacco carcinogenesis. Using MT-ATP6 as the experimentally validated housekeeping gene, the highest extrahepatic expression of UGT2B genes was observed in human tonsil, with UGT2B expression levels similar to that observed in human liver. UGT2B17 exhibited high relative expression in most tissues examined, including lung, most tissues of the aerodigestive tract, and pancreas. UGT2B7 expression was highest in pancreas but low or undetectable in most other tissues examined. UGT2B10 expression was high in both tonsil and tongue. There was wide variability between individuals in the magnitude of expression in each tissue site, and there were strong correlations between UGT2B expression levels in different individuals within many of the tissue sites, suggesting coordinated regulation of UGT2B gene expression in extrahepatic tissues. In the liver, UGTs 2B4, 2B7, 2B10, and 2B15 were significantly correlated with each other (all r(2) > 0.70, P < 0.0001). In all examined tissues of the aerodigestive tract, UGTs 2B10, 2B11, and 2B17 exhibited a strong correlation with each other (all r(2) > 0.75, P < 0.05). UGTs 2B7 and 2B10 exhibited a strong inverse correlation in the pancreas (r(2) = -0.95, P < 0.01). These data suggest that specific UGT2B enzymes important in tobacco carcinogen metabolism are expressed and coordinately regulated in various target sites for tobacco-related cancers.

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Title: UGT2B gene expression analysis in multiple tobacco carcinogen-targeted tissues
Creators: Nathan R Jones - Department of Pharmacology, Pennsylvania State College of Medicine, Hershey, Pennsylvania (N.R.J.); and Department of Pharmaceutical Sciences, Washington State University College of Pharmacy, Spokane, Washington (P.L.)
Philip Lazarus
Publication Details: Drug metabolism and disposition, Vol.42(4), pp.529-536
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: R01 DE013158 / NIDCR NIH HHS R01-DE13158 / NIDCR NIH HHS
Identifiers: 99900547219101842
Language: English
Resource Type: Journal article