<p>Epigenetic alterations have emerged as critical factors in the pathogenesis of brain cancer, particularly gliomas. This article explores the impact of organochlorine pesticides (OCPs) on the hypermethylation of key tumor suppressor genes, and some histone modifications in primary brain tumor (PBT) patients. This study involved 73 patients diagnosed with PBT and 15 non-cancerous brain tissue samples as contol. DNA extracted from tumor specimens was used to evaluate the methylation status of tumor suppressor genes, <i>P16</i> and <i>RRP22</i>, using the methylation-specific PCR (MSP) technique and four histone marks (H4K16ac, H3K9ac, H4K20me3, and H3k4me2) to investigate by western blotting. The results of MSP revealed the methylation of <i>RRP22</i> and <i>P16</i> promoter regions and western blot analysis demonstrated significantly low levels of H3K9ac, H4K20me3, and H3K4me2 in PBT patients in comparison with the controls. The results of regression analysis revealed direct and significant correlations between serum OCPs concentration and methylation of <i>RRP22</i> and <i>P16</i>. Furthermore, a direct and significant association was observed between hypomethylation of histones H3K4 and H4K20, as well as hypoacetylation of H3K9, with OCPs levels. This study revealed that epigenetic modifications play a significant role in the development of brain tumors, with OCPs identified as key contributors to these changes. Our research indicated that in patients with PBT, hypermethylation of the <i>RRP22</i> and <i>P16</i> gene and histone modifications correlates directly and significantly with the levels of OCPs found in their serum.</p> Graphical Abstract <p>Organochlorine pesticides exposure and epigenetic modifications in brain cancer: This study reveals that pesticide exposure may significantly induce the epigenetic modifications and by this way, participate in primary brain cancer development.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Organochlorine Pesticides and Epigenetic Alterations in Brain Cancer

  • Fatemeh Yousefi,
  • Gholamreza Asadikaram,
  • Saeid Karamouzian,
  • Moslem Abolhassani,
  • Hossein Pourghadamyari,
  • Vahid Moazed

摘要

Epigenetic alterations have emerged as critical factors in the pathogenesis of brain cancer, particularly gliomas. This article explores the impact of organochlorine pesticides (OCPs) on the hypermethylation of key tumor suppressor genes, and some histone modifications in primary brain tumor (PBT) patients. This study involved 73 patients diagnosed with PBT and 15 non-cancerous brain tissue samples as contol. DNA extracted from tumor specimens was used to evaluate the methylation status of tumor suppressor genes, P16 and RRP22, using the methylation-specific PCR (MSP) technique and four histone marks (H4K16ac, H3K9ac, H4K20me3, and H3k4me2) to investigate by western blotting. The results of MSP revealed the methylation of RRP22 and P16 promoter regions and western blot analysis demonstrated significantly low levels of H3K9ac, H4K20me3, and H3K4me2 in PBT patients in comparison with the controls. The results of regression analysis revealed direct and significant correlations between serum OCPs concentration and methylation of RRP22 and P16. Furthermore, a direct and significant association was observed between hypomethylation of histones H3K4 and H4K20, as well as hypoacetylation of H3K9, with OCPs levels. This study revealed that epigenetic modifications play a significant role in the development of brain tumors, with OCPs identified as key contributors to these changes. Our research indicated that in patients with PBT, hypermethylation of the RRP22 and P16 gene and histone modifications correlates directly and significantly with the levels of OCPs found in their serum.

Graphical Abstract

Organochlorine pesticides exposure and epigenetic modifications in brain cancer: This study reveals that pesticide exposure may significantly induce the epigenetic modifications and by this way, participate in primary brain cancer development.