AI Article Synopsis

  • - Phthalates, specifically di-(2-ethylhexyl) phthalate (DEHP), are linked to changes in thyroid function, and this study explored how DEHP affects DNA damage and cell growth in thyroid cancer cells and juvenile rats.
  • - Results showed that exposure to DEHP increased cell proliferation and caused DNA damage, identifiable by the activation of γH2AX, particularly at higher concentrations in both cell cultures and animal models.
  • - The research indicated that DEHP's effects are mediated through the activation of thyrotropin receptor (TSHR) signaling pathways, highlighting the potential endocrine-disrupting effects of phthalates on thyroid health.

Article Abstract

Phthalates are being suggested to be associated with altered thyroid function and proliferative changes, but detailed mechanisms remain unclear. Here, we examined the effects of di-(2-ethylhexyl) phthalate (DEHP) on DNA damage and proliferation in thyroid using thyroid carcinoma cell line, 8505C, in vitro and the rats orally treated with DEHP at 0, 0.3, 3, 30 and 150 mg/kg for 90 days from post-natal day 9 in vivo. Exposure to DHEP (1-50 μM) induced cellular proliferation, as evidenced by increased cell viability and DNA synthesis. Activation of γH2AX, a sensitive biomarker for DNA damage was observed following the exposure to DHEP (from 5 to 50 μM) with increased comet tail moment (5-100 μM) in comet assay, reflecting that DNA damage also occurred. When upstream signaling was examined, both thyrotropin receptor (TSHR)-ERK1/2 axis and TSHR-AKT axis were activated with upregulation of Pax8, a master transcriptional factor for thyroid differentiation and proliferation. Thyroid tissue from juvenile rats orally exposed to DEHP also confirmed DNA damage responses and the activation of TSHR signaling, which was evident from 0.3 to 3 mg/kg respectively. Notably, deletion of TSHR through siRNA attenuated these DEHP-induced events in vitro. Collectively these results suggest that DEHP induces DNA damage and cellular proliferation in thyroid, which appears to be from TSHR activation, providing an important insight into endocrine disrupting activities of phthalates on thyroid.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fct.2018.12.010DOI Listing

Publication Analysis

Top Keywords

dna damage
24
proliferation thyroid
12
thyroid
8
rats orally
8
exposure dhep
8
cellular proliferation
8
dna
7
damage
6
proliferation
5
di-2-ethylhexylphthalate promotes
4

Similar Publications

PsDMAP1/PsTIP60-regulated H4K16ac is required for ROS-dependent virulence adaptation of on host plants.

Proc Natl Acad Sci U S A

January 2025

Department of Plant Pathology, College of Plant Protection, China Agricultural University, Beijing 100193, China.

Host plants and various fungicides inhibit plant pathogens by inducing the release of excessive reactive oxygen species (ROS) and causing DNA damage, either directly or indirectly leading to cell death. The mechanisms by which the oomycete manages ROS stress resulting from plant immune responses and fungicides remains unclear. This study elucidates the role of histone acetylation in ROS-induced DNA damage responses (DDR) to adapt to stress.

View Article and Find Full Text PDF

ANAC044 orchestrates mitochondrial stress signaling to trigger iron-induced stem cell death in root meristems.

Proc Natl Acad Sci U S A

January 2025

Ministry of Education Key Laboratory of Environment Remediation and Ecological Health, Zhejiang Provincial Key Laboratory of Agricultural Resources and Environment, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.

While iron (Fe) is essential for life and plays important roles for almost all growth related processes, it can trigger cell death in both animals and plants. However, the underlying mechanisms for Fe-induced cell death in plants remain largely unknown. S-nitrosoglutathione reductase (GSNOR) has previously been reported to regulate nitric oxide homeostasis to prevent Fe-induced cell death within root meristems.

View Article and Find Full Text PDF

HCAR2 Modulates the Crosstalk between Mammary Epithelial Cells and Macrophages to Mitigate Staphylococcus aureus Infection in the Mouse Mammary Gland.

Adv Sci (Weinh)

January 2025

State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China.

Staphylococcus aureus (S. aureus) is a major zoonotic pathogen, with mammary gland infections contributing to mastitis, a condition that poses significant health risks to lactating women and adversely affects the dairy industry. Therefore, understanding the immune mechanisms underlying mammary infections caused by S.

View Article and Find Full Text PDF

ATRX mutation modifies the DNA damage response in glioblastoma multiforme tumor cells and enhances patient prognosis.

Medicine (Baltimore)

January 2025

Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.

The presence of specific genetic mutations in patients with glioblastoma multiforme (GBM) is associated with improved survival outcomes. Disruption of the DNA damage response (DDR) pathway in tumor cells enhances the effectiveness of radiotherapy drugs, while increased mutational burden following tumor cell damage also facilitates the efficacy of immunotherapy. The ATRX gene, located on chromosome X, plays a crucial role in DDR.

View Article and Find Full Text PDF

Flap endonuclease 1 repairs DNA-protein cross-links via ADP-ribosylation-dependent mechanisms.

Sci Adv

January 2025

Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD 20892, USA.

DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They are ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading to neurodegeneration and cancer. The type, structure, and repair of FA-induced DPCs remain largely unknown.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!