Polymer-based restorative materials are widely used in dentistry. Cured materials contain unpolymerized methacrylate monomers which leak into the oral environment. Several studies have described adverse biological effects including apoptosis in vitro after short term exposure to relatively high concentrations of the leachable hydroxyethyl methacrylate (HEMA). The mechanisms involved in the cytotoxic effects of HEMA have not been fully elucidated although involvement of various signaling pathways including oxidative damage, activation of MAP-kinases as well as caspases has been suggested. Involvement of reactive oxygen species (ROS) formation is supported by our previous finding that HEMA influence intracellular levels of glutathione which play a dominant role in protection against oxidative damage. To further elucidate mechanisms involved in toxic responses induced by HEMA, we exposed the cell line BEAS 2B to a “sub lethal” concentration of 2 mM HEMA for 4 hours and subsequently isolated mRNA for analysis of the mRNA expression profile (transcriptomics). The results showed that EMA clearly, but not only, induced increased mRNA levels of Ovary, Kidney and Liver Protein 38 (OKL38), Heme Oxygenase 1 (HMOX1), Thioredoxin Reductase1 (TXRND1) and Glutamate-Cysteine Ligase, Modifier subunit (GCLM). We have previously shown that HEMA induces expression of tumor suppressor protein p53. OKL38 has been identified as a downstream target of p53 with a possible role in regulating cell death in concordance with p53. OKL38 has also been shown to be an oxidative stress response gene stimulated by oxidized phospholipids. Furthermore, HMOX1 and TXNRD1 encode proteins associated with protection against oxidative stress whereas GCLC encodes the first rate limiting enzyme of glutathione synthesis. Overall, our results support that HEMA causes oxidative damage followed by activation of genes involved in protection against oxidative stress in the BEAS 2B cell line.
Exposure to Dental Monomer Hydroxyethyl Methacrylate (HEMA) Induces Increased Transcription of Genes Involved in Oxidative Stress Responses
Becker R, Rukke HV, Dahl JE, Samuelsen JT.
Toxicologist 2016; 150: 341 (abstract 2444)