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 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 N2 -(1-methylpyrenyl)-2'-deoxyguanosine and N6 -(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.
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