Phthalates are classified as non-genotoxic carcinogens. These compounds do not cause direct DNA damage but may induce indirect DNA lesions leading to cancer development. In the presented paper we have studied the effect of di-n-butyl phthalate (DBP), butylbenzyl phthalate (BBP), and their metabolites, such as mono-n-butyl phthalate (MBP) and monobenzyl phthalate (MBzP) on selected epigenetic parameters in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with tested phthalates at 0.001, 0.01 and 0.1 μg/mL for 24 h. Next, global DNA methylation, methylation in the promoter regions of tumor suppressor genes (P16, TP53) and proto-oncogenes (BCL2, CCND1) were assessed as well as the expression profile of the indicated genes was analysed. The obtained results have revealed significant reduction of global DNA methylation level in PBMCs exposed to BBP, MBP and MBzP. Phthalates changed methylation pattern of the tested genes, decreased expression of P16 and TP53 genes and increased the expression of BCL2 and CCND1. In conclusion, our results have shown that the examined phthalates disturbed the processes of methylation and expression of tumor suppressor genes (P16, TP53) and protooncogenes (BCL2, CCND1) in human PBMCs.
Keywords: DNA methylation; Epigenetic alterations; Gene expression; Human peripheral blood mononuclear cells; Non-genotoxic carcinogens; Phthalates.
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