Effect of Perfluorooctanoic Acid on the Epigenetic and Tight Junction Genes of the Mouse Intestine (original) (raw)
Related papers
International Journal of Toxicology, 2021
Perfluorooctanoic acid (PFOA) is a widespread contaminant in the environment, that is, implicated in several toxicities. The intestinal wall is first surface of interaction with any toxicant after exposure through the oral route. Previous studies have demonstrated: increased intestinal bioaccumulation of PFOA in different experimental animals, PFOA-induced changes in DNA methylation of several tissues, and alterations in expression of tight junction (TJ) genes due to epigenetics changes. Nevertheless, evidence on the toxicity of PFOA on intestinal epigenetics and TJ genes is limited. Thus, the present work investigates PFOA-induced changes in expression of epigenetic genes of the colon in relation to TJ genes alterations. CD-1 mice were orally dosed with 4 different concentrations of PFOA (1, 5, 10, or 20 mg/kg/d) for 10 consecutive days, and its bioaccumulation and induced changes in the expression of TJ and epigenetic genes in the colon were investigated. The PFOA was accumulated in very high concentrations in the colon tissue and decreased the expression levels of DNA methyltransferase genes (Dnmt3a and DNMT3b). However, no significant alterations were observed in expression levels of 10-11 translocation (TET1 and TET2) genes. We also found a significant reduction in the mRNA expression of TJ protein-1 (TJP1) at the highest concentration of PFOA. Furthermore, the mRNA expression levels were significantly increased for occludin (OCLN) and Claudins (CLDN2, CLDN3, CLDN8) genes at higher concentrations. Therefore, our study demonstrates that PFOA initiates DNA methylation alterations and changes the expression of genes necessary for preserving the integrity of the colon barrier.
Gene profiling in the livers of wild-type and PPARalpha-null mice exposed to perfluorooctanoic acid
Toxicologic pathology, 2008
Health concerns have been raised because perfluorooctanoic acid (PFOA) is commonly found in the environment and can be detected in humans. In rodents, PFOA is a carcinogen and a developmental toxicant. PFOA is a peroxisome proliferator-activated receptor alpha (PPARalpha) activator; however, PFOA is capable of inducing heptomegaly in the PPARalpha-null mouse. To study the mechanism associated with PFOA toxicity, wild-type and PPARalpha-null mice were orally dosed for 7 days with PFOA (1 or 3 mg/kg) or the PPARalpha agonist Wy14,643 (50 mg/kg). Gene expression was evaluated using commercial microarrays. In wild-type mice, PFOA and Wy14,643 induced changes consistent with activation of PPARalpha. PFOA-treated wild-type mice deviated from Wy14,643-exposed mice with respect to genes involved in xenobiotic metabolism. In PFOA-treated null mice, changes were observed in transcripts related to fatty acid metabolism, inflammation, xenobiotic metabolism, and cell cycle regulation. Hence, a c...
Nephrotoxicity of Perfluorooctane Sulfonate (PFOS) -Effect on Transcription and Epigenetic Factors
Environmental Epigenetics, 2022
Perfluorooctane sulfonate (PFOS) is a widespread persistent environmental pollutant implicated in nephrotoxicity with altered metabolism, carcinogenesis, and fibrosis potential. We studied the underlying epigenetic mechanism involving transcription factors of PFOS induced kidney injury. A 14-day orally dosed mouse model was chosen to study acute influences in vivo. mRNA expression analysis and gene set enrichment analysis were performed to elucidate the relationship between epigenetic regulators, transcription factors, kidney disease, and metabolism homeostasis. PFOS was found to accumulate in mouse kidney in a dose-dependent manner. Kidney injury markers Acta2 and Bcl2l1 increased in expression significantly. Transcription factors including Nef2l2, Hes1, Ppara, and Ppard were upregulated while Smarca2 and Pparg were downregulated. Further, global DNA methylation levels decreased and the gene expression of histone demethylases Kdm1a, Kdm4c were upregulated. Our work implicates PFOS-induced gene expression alterations in epigenetics, transcription factors, and kidney biomarkers with potential implications in kidney fibrosis and kidney carcinogenesis. Future experiments can focus on epigenetic mechanisms to establish a panel of PFOS-induced biomarkers for nephrotoxicity evaluation.
Toxics, 2020
Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible toxicity and toxicity routes of these compounds. We report that these compounds have the potential to cause epigenetic modifications, and to induce dysregulation in the cell proliferation cycle as well as apoptosis in A549 lung cancer cells when exposed to 10-, 200- and 400 μM concentrations of each compound. Our studies show that exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may cause hypomethylation in the epigenome, but changes in the epigenetic makeup are not evident upon exposure to GenX. We establish that exposure to lower doses of these compounds causes the cells’ balance to shift to cell proliferation, whereas exposure to higher concentrations shifts the balanc...