The effect of benzo[alpha]pyrene on DNA methylation and telomerase activity in human normal and cancer cells

Zarei, Reza and Moghadam, Delaram and MoradiSarabi, Mostafa and Naghibalhossaini, Fakhraddin (2022) The effect of benzo[alpha]pyrene on DNA methylation and telomerase activity in human normal and cancer cells. Toxicology in Vitro.

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Abstract

Benzo[a]pyrene (BaP) exposure has been associated with an increased risk of carcinogenesis. We investigated the effects of BaP on cell viability, the promoter methylation of 11 tumor-associated genes, the global DNA methylation, and telomerase enzyme activity in 5 human cancer cell lines (HCT116, PC3, MDA-MB-231, A549, and HepG2) and normal human peripheral blood mononuclear cells (PBMCs) and adipose-derived mesenchymal stem cells (AD-MSCs). BaP inhibited the proliferation of cells in a dose-dependent manner, as measured by MTT assay. Human normal cells were more sensitive to BaP cytotoxicity than cancer cells. After treatment with the minimally toxic concentration of BaP (5 μM for 72 h), 3 differentially methylated genes (genes with different promoter methylation status) were identified between BaP-treated and untreated control cells, as verified by MSP analysis. BaP induced hypomethylation of COX-2 and MSH2 in normal PBMCs and hypermethylation of APC in HCT116 CRC cells. BaP also non-significantly decreased global methylation levels in 3 cancer cell lines (HCT16, PC3, and A549), as measured by ELISA assay. BaP also reduced telomerase enzyme activity in human AD-MSC cells in a dose-dependent manner. To our knowledge, this is the first report of BaP-effects on telomerase activity and DNA methylation in human normal and cancer cells.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: samira sepahvandy
Date Deposited: 19 Feb 2022 04:21
Last Modified: 19 Feb 2022 04:21
URI: http://eprints.lums.ac.ir/id/eprint/3664

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