Shu-Yi Gu, Tian Feng, Fang-Yin Gang, Si-Yu Yu, Wan Chan, Zhao-Cheng Ma, Yao-Hua Gu, Bi-Feng Yuan
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Perfluorooctanoic acid (PFOA) is a highly bioaccumulative environmental endocrine disruptor and a persistent organic pollutant. Epigenetic modifications in DNA and RNA are crucial for regulating gene expression and are involved in numerous physiological processes. However, research on the effects of PFOA on epigenetic modifications is still limited. In this study, we systematically investigated the alterations in epigenetic modifications in both DNA and RNA from the heart, liver, spleen, lung, kidney, and brain of C57BL/6N mice following exposure to PFOA at doses of 0, 0.5, and 5 mg kg-1 d-1, utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results indicated that exposure to PFOA inhibited weight gain in mice, and significant changes were observed in the organ coefficients of the liver, spleen, lungs, and heart in the high PFOA exposure group. Modifications in DNA and RNA exhibited tissue specificity. Orthogonal partial least squares discriminant analysis revealed that the control group and the high PFOA exposure group clustered well, suggesting that PFOA exposure significantly impacts epigenetic modifications in DNA and RNA. Specifically, PFOA exposure significantly affected the levels of 5-hydroxymethylcytosine (5hmC) in genomic DNA in the heart, lung, kidney, and liver tissues. For RNA modifications, significant changes were observed, with the levels of 12, 13, 10, 6, 12, and 14 modifications in the heart, liver, spleen, lung, kidney, and brain, respectively, altered in response to PFOA exposure. Our study highlights the significance of PFOA exposure in altering DNA and RNA modifications, providing a new perspective on understanding the toxicology of PFOA from an epigenetic standpoint.