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Author Spotlight: In Vivo Assessment of Thyroid Hormone Disruption Using the THAI Mouse Model
Published on: October 6, 2023
Organochlorine pesticides and epigenetic alterations in thyroid tumors
Fouzieh Salimi1,2,3, Gholamreza Asadikaram2,3, Mohammad Reza Ashrafi2,3
1Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences Kerman University of Medical Sciences, Kerman, Iran.
Purpose:
Cancer incidence depends on various factors e.g., pesticide exposures which cause epigenetic alterations. The present research aimed to investigate the organochlorine pesticides (OCPs) impacts on promoter methylation of three tumor-suppressor genes and four histone modifications in thyroid nodules in 61 Papillary thyroid carcinoma (PTC) and 70 benign thyroid nodules (BTN) patients.
Methods:
OCPs were measured by Gas chromatography. To identify promoter methylation of TSHR, ATM, and P16 genes, the nested-methylation-specific PCR (MSP) was utilized, and histone lysine acetylation (H3K9, H4K16, and H3K18) and lysine methylation (H4K20) were detected by performing western blot analysis.
Results:
Further TSHR methylation and less P16 methylation were observed in PTC than in BTN. No substantial difference was detected for ATM methylation between PTC and BTN groups. Also, OCP dramatically increased the odds ratio of TSHR (OR=3.98, P=0.001) and P16 (OR=5.65, P<0.001) methylation while confounding variables reduced the chances of ATM methylation arising from 2,4-DDE and 4,4-DDT influence. Hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18 (P<0.001) were observed in PTC samples than BTN. Furthermore, OCPs substantially decreased the odds ratio of H3K9 (OR=3.68, P<0.001) and H4K16 (OR=6.03, P<0.001) acetylation.
Conclusion:
The current research indicated that OCPs could contribute to PTC progression by TSHR promoter hypermethylation and decreased acetylation of H3K9 and H4K16. In addition, in PTC patients, assessing TSHR promoter methylation and acetylation of H3K9 and H4K16 could have predictive values.
Insights
Organochlorine pesticides (OCPs) exposure is linked to papillary thyroid carcinoma (PTC) progression. OCPs increase TSHR methylation and decrease H3K9/H4K16 acetylation, suggesting predictive value in PTC patients.
Area of Science:
- Environmental Epigenetics
- Cancer Biology
- Toxicology
Background:
- Cancer incidence is influenced by environmental factors like pesticide exposure, which can induce epigenetic alterations.
- Organochlorine pesticides (OCPs) are persistent environmental pollutants with potential links to various health issues, including cancer.
Purpose of the Study:
- To investigate the impact of organochlorine pesticides (OCPs) on the promoter methylation of three tumor-suppressor genes (TSHR, ATM, P16) and four histone modifications in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTN).
Main Methods:
- OCPs were quantified using Gas Chromatography.
- Promoter methylation of TSHR, ATM, and P16 genes was assessed via nested-methylation-specific PCR (MSP).
- Histone modifications, including acetylation (H3K9, H4K16, H3K18) and methylation (H4K20), were detected using Western blot analysis.
Main Results:
- Papillary thyroid carcinoma (PTC) samples showed increased TSHR promoter methylation and decreased P16 methylation compared to benign thyroid nodules (BTN).
- Organochlorine pesticide (OCP) exposure significantly increased the odds of TSHR and P16 methylation.
- PTC samples exhibited hypomethylation of H4K20 and hypo-acetylation of H3K9, H4K16, and H3K18, with OCPs decreasing the odds of H3K9 and H4K16 acetylation.
Conclusions:
- Organochlorine pesticides (OCPs) may contribute to papillary thyroid carcinoma (PTC) progression through TSHR promoter hypermethylation and reduced H3K9/H4K16 acetylation.
- Assessing TSHR promoter methylation and H3K9/H4K16 acetylation in PTC patients may offer predictive value for the disease.
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