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Impact of p53 function on the sulfotransferase‐mediated bioactivation of the alkylated polycyclic aromatic hydrocarbon 1‐hydroxymethylpyrene in vitro
Author(s) -
Wohak Laura E.,
Monien Bernhard,
Phillips David H.,
Arlt Volker M.
Publication year - 2019
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.22299
Subject(s) - deoxyadenosine , carcinogen , chemistry , deoxyguanosine , sulfotransferase , dna , mutagen , adduct , dna damage , biochemistry , in vitro , cell culture , enzyme , microbiology and biotechnology , biology , genetics , organic chemistry
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 as 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 hr. 1‐HMP‐DNA adduct formation was determined by ultraperformance liquid chromatography‐tandem mass spectrometry analysis, which quantified two nucleoside adducts N 2 ‐(1‐methylpyrenyl)‐2′‐deoxyguanosine and N 6 ‐(1‐methylpyrenyl)‐2′‐deoxyadenosine. 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. Environ. Mol. Mutagen., 60:752–758, 2019. © 2019 Wiley Periodicals, Inc.