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Impact of p53 function on the sulfotransferase-mediated bioactivation of the alkylated polycyclic aromatic hydrocarbon 1-hydroxymethylpyrene in vitro

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)752-758
Number of pages7
JournalEnvironmental and Molecular Mutagenesis
Volume60
Issue number8
Early online date18 May 2019
DOIs
Publication statusPublished - 1 Oct 2019

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© 2019 Wiley Periodicals, Inc.

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Abstract

The tumor suppressor p53, encoded by TP53, is known as the 'guardian of the genome'. Sulfotransferases (SULTs) are involved in the metabolism of alkylated polycyclic aromatic hydrocarbons such 1-hydroxymethylpyrene (1-HMP) which is a known substrate for SULT1A1. To investigate the impact of TP53 on the metabolic activation of 1-HMP a panel of isogenic human colorectal HCT116 cells having TP53(+/+), TP53(+/-) or TP53(-/-) were treated with 10 μM 1-HMP for 24 hours. 1-HMP-DNA adduct formation was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, which quantified two nucleoside adducts N2 -(1-methylpyrenyl)-2'-deoxyguanosine (MPdG) and N6 -(1-methylpyrenyl)-2'-deoxyadenosine (MPdA). 1-HMP treatment resulted in significantly (~40-fold) higher DNA adduct levels in TP53(+/+) cells than in the other cell lines. Higher levels of 1-HMP-induced DNA adducts in TP53(+/+) cells correlated with higher basal expression of SULT1A1/3 in this cell line but 1-HMP treatment showed no effect on the expression of this protein. These results indicate that the cellular TP53 status is linked to the SULT1A1/3-mediated bioactivation of 1-HMP thereby broadening the spectrum of p53's targets. This article is protected by copyright. All rights reserved.

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