Organochlorine Pesticides and Epigenetic Alterations in Brain Cancer.

Abstract

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.