Inhibition of TEGDMA and HEMA-induced genotoxicity and cell cycle arrest by N-acetylcysteine.
OBJECTIVE
Dental resin monomers like triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are able to cause an imbalance of the redox state in mammalian cells. The resulting oxidative stress originating from reactive oxygen species (ROS) has been associated with cytotoxicity. We hypothesized that ROS might contribute to the generation of genotoxicity by TEGDMA and HEMA as well. Therefore, we examined the formation of micronuclei in V79 cells by both resin monomers in the presence of the antioxidant N-acetylcysteine (NAC), which scavenges ROS. In addition, we analyzed the effects of TEGDMA and HEMA on the normal cell cycle in the presence of NAC.


METHODS
V79 fibroblasts were exposed to increasing concentrations of TEGDMA and HEMA in the presence and absence of NAC for 24h. Genotoxicity was indicated by the formation of micronuclei. The modification of the normal cell cycle was analyzed by flow cytometry (FACS).


RESULTS
A dose-related increase in the number of micronuclei in V79 cells-induced by TEGDMA and HEMA indicated genotoxicity of both chemicals. However, the formation of micronuclei was reduced in the presence of 10 mmol/L NAC, indicating its protective role. A cell cycle delay in G2 phase caused by TEGDMA was absent when cells were co-treated with NAC. Similarly, the presence of NAC led to a reversion of the cell cycle delay in HEMA-treated cell cultures.


CONCLUSIONS
Our results suggest that genotoxic effects and the modification of the cell cycle caused by TEGDMA and HEMA are mediated, at least in part, by oxidative stress.
Schweikl
H
H
Department of Operative Dentistry and Periodontology, University of Regensburg, D-93042 Regensburg, Germany. helmut.schweikl@klinik.uni-regensburg.de
Hartmann
A
A
Hiller
K-A
KA
Spagnuolo
G
G
Bolay
C
C
Brockhoff
G
G
Schmalz
G
G
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D003188:Composite Resins / Q000633:toxicity*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008689:Methacrylates / Q000633:toxicity*; D015162:Micronucleus Tests; D018384:Oxidative Stress / Q000187:drug effects; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000633:toxicity
D000975:Antioxidants; D003188:Composite Resins; D016166:Free Radical Scavengers; D008689:Methacrylates; D011109:Polymethacrylic Acids; D017382:Reactive Oxygen Species; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; C005044:hydroxyethyl methacrylate; D000111:Acetylcysteine