全氟辛基酸 (PFOA) 在环境中具有持久性，并被国际癌症研究机构 (IARC) 归类为可能的人类胰腺致癌物质。本研究使用 RT-PCR 和 ELISA 技术研究了表观遗传变异、内质网应激相关和代谢相关基因的表达水平变化以及 DNA 甲基转移酶表达情况。PFOA 显著增加了甲基化水平 (5-mC%)，影响了 DNA 甲基化维持基因的表达，并降低了脂质代谢相关基因，除了 PPARγ（增加≥13倍）。虽然 PFOA 诱导了 ATF4（增加≥ 5.41 倍）和 CHOP（增加≥ 5.41 倍）基因的表达，但抑制了 ATF6（≥ 67.2%）、GRP78（≥ 64.3%）、Elf2α（≥ 95.8%）、IRE1（≥ 95.5%）和 PERK （≥ 91.7%）基因的表达。认为表观遗传机制以及葡萄糖-脂质代谢紊乱和内质网应激相关基因变化可能在 PFOA 诱导的胰腺毒性中发挥了关键作用。版权所有 © 2023 Elsevier B.V.。

Perfluorooctanoic acid (PFOA) is environmentally persistent and has been classified by The International Cancer Research Agency (IARC) as a possible human pancreatic carcinogen. In this study, the epigenetic alteration, the changes in the expression levels of endoplasmic reticulum stress-related and metabolism-related genes, as well as DNA methyltransferase expression were investigated using RT-PCR and ELISA assays. PFOA induced a significant increase in the methylation ratio (5-mC%), impacted DNA methylation maintenance gene expression and decreased lipid metabolism-related genes except for PPARγ (≥ 13-fold increase). While PFOA induced the expression of ATF4 (≥ 5.41-folds), CHOP (≥ 5.41-folds) genes, it inhibited the expression of ATF6 (≥ 67.2%), GRP78 (≥ 64.3%), Elf2α (≥ 95.8%), IRE1 (≥ 95.5%), and PERK (≥ 91.7%) genes. It is thought that epigenetic mechanisms together with disruption in the glucose-lipid metabolism and changes in endoplasmic reticulum stress-related genes may play a key role in PFOA-induced pancreatic toxicity.Copyright © 2023 Elsevier B.V. All rights reserved.