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.

中文翻译：

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p53功能对磺基转移酶介导的烷基化多环芳烃1-羟甲基py体外生物活化的影响。

由TP53编码的抑癌基因p53被称为“基因组守护者”。磺基转移酶（SULTs）参与烷基化多环芳烃的代谢，例如1-羟甲基py（1-HMP），这是SULT1A1的已知底物。为了研究TP53对1-HMP代谢激活的影响，用10μM处理一组具有TP53（+ / +），TP53（+/-）或TP53（-/-）的同基因人结肠直肠HCT116细胞1-HMP 24小时。通过超高效液相色谱-串联质谱分析法确定了1-HMP-DNA加合物的形成，该定量分析了两个核苷加合物N2-（1-甲基吡啶基）-2'-脱氧鸟苷和N6-（1-甲基吡啶基）-2'-脱氧腺苷。1-HMP处理导致TP53（+ / +）细胞中的DNA加合物水平明显高于其他细胞系（约40倍）。TP53（+ / +）细胞中较高水平的1-HMP诱导的DNA加合物与该细胞系中SULT1A1 / 3的较高基础表达相关，但是1-HMP处理对该蛋白的表达没有影响。这些结果表明，细胞TP53的状态与SULT1A1 / 3介导的1-HMP的生物激活有关，从而拓宽了p53靶标的范围。环境。大声笑 Mutagen。，60：752-758，2019.©2019 Wiley Periodicals，Inc.