Modulação epigenética induzida pelo reteno: avaliação do perfil de metilação global em células pulmonares não neoplásicas e neoplásicas

Abstract

This study investigated the epigenetic effects of Retene (RET), a polycyclic aromatic hydrocarbon (PAH) widely used as a marker of biomass burning, on non-neoplastic (BEAS-2B) and neoplastic (A549) human lung cells. The cytotoxicity of the compound was evaluated using the MTT assay at environmentally relevant concentrations (10, 30, and 60 ng/mL) and higher concentrations (up to 480 ng/mL) at 24, 48, and 72 hours. The results showed that RET did not exhibit cytotoxicity under any of the tested conditions. Subsequently, the global DNA methylation profile was evaluated by ELISA immunoassay, revealing marked and statistically significant (p < 0.0001) global hypomethylation in both cell lines, regardless of concentration or exposure time. Additionally, RNA sequencing data analysis from BEAS-2B cells exposed to 32 ng/mL of RET revealed trends of gene expression repression in the DNA methyltransferase (DNMT) and Ten-Eleven Translocation (TET) demethylase enzyme families at 24 hours, with inversion to positive values at 72 hours, indicating a trend of increased gene expression, although without statistical significance. These findings may point to post-transcriptional mechanisms as likely mediators of the observed hypomethylation, including post-translational modifications of DNMTs, oxidative stress, and miRNA regulation. Taken together, the results broaden the understanding of RET toxicity, positioning it not only as a documented genotoxic agent but also as an epigenetic modulator.