Inhibition of telomerase activity in HL-60 cell line by methacrylic monomers

Methacrylic compounds, like bis-phenol A glycerolate dimethacrylate (Bis-GMA), triethyleneglycol-dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), urethane-dimethacrylate (UDMA) and 1,4-butanediol dimethacrylate (BDDMA) are used as polymerizable components of composite resins and some cements utilized in dentistry and in other medical fields. After performing dental restorations, amounts of uncured monomers are released either into the oral cavity or in pulpal tissues whence they can leach into the blood circulation causing, or contributing to, local or systemic adverse effects. Since the intracellular mechanisms of the aforesaid effects are still not completely clear, many in vitro studies with methacrylic monomers have been performed in the attempt to explain them. These studies have underlined that monomers display genotoxic, allergenic, cytotoxic, estrogenetic and mutagenic activity. Moreover, these monomers alter lipid metabolism, glutathione concentration, reactive oxygen species production, energy metabolism cell cycle and behave as differentiating agents on human promyelocytic HL-60 cell line. The last property was especially intriguing because HL-60 cells possess high telomerase activity, a phenotype related to their immortalized status. Telomerase, adding telomeric repeats to the 3'-end of telomeres, protects chromosomes from the telomeric attrition associated with the 'end-replication problem'. Telomerase activity is present in human stem cells, progenitor cells, and germ cells but is undetectable in the vast majority of adult somatic tissues. During cell differentiation telomerase looses its function of synthesis and maintenance of the telomeric units. In this work, we verified whether the differentiation of HL-60 cells, induced by Bis-GMA, HEMA, TEGDMA, UDMA or BDDMA, is also accompanied by a decrease of telomerase activity. The results show that all monomers and all-trans-retinoic acid (ATRA) - used as positive control - induce cell differentiation. Moreover, cells treated with TEGDMA, HEMA, UDMA, BDDMA or ATRA display a decrease of telomerase activity (about 50%) in respect to untreated cells. On the contrary, Bis-GMA does not provoke any alteration of enzymatic activity. These observations suggest that the ability of some methacrylic monomers to induce differentiation of promyelocytic leukemia cells may be mediated by their capacity to determine a down-regulation of telomerase activity.