Influence of TEGDMA on the mammalian cell cycle in comparison with chemotherapeutic agents.
OBJECTIVE
The dental resin monomer triethylene glycol dimethacrylate (TEGDMA) caused a cell cycle arrest in response to DNA damage. However, the underlying mechanisms are unclear. Therefore, the influence of TEGDMA on the cell cycle was analyzed in comparison with the chemotherapeutic agents adriamycin and mitomycin C (MMC), which arrest the cell cycle through different mechanisms.


METHODS
RAW264.7 mouse macrophages were exposed to TEGDMA, adriamycin, or MMC, and flow cytometry (FACS) was used for cell cycle analyses. In addition, the number of surviving cells was determined by a crystal violet assay, and viability in treated cultures was determined by FACS after staining of cells with trypan blue. Morphological changes in cells were interpreted using forward and side scatter (FSC/SSC) cell physical criteria.


RESULTS
The exposure of cells to 1mM TEGDMA resulted in a delay of the cell cycle in G1 phase since 85.3% of the cells were found in G1 compared with 47.4% in untreated controls. Adriamycin also increased the number of cells (72.1%) in G1 compared to controls. Caffeine, an inhibitor of the checkpoint kinases ATM (ataxia telangiectasia-mutated) and ATR (ATM and Rad3-related), had no effect on the TEGDMA and adriamycin-induced cell cycle arrest. In contrast, MMC delayed the cell cycle in G2 since cell numbers increased to 22.1% compared to 10.7% in controls. The effect of MMC on G2 was even increased by low caffeine concentrations (100-400muM), but 1000muM caffeine inhibited MMC activity.


CONCLUSIONS
Our results suggest that the mechanism of a TEGDMA-induced arrest of the cell cycle is different from the effect of the direct-acting interstrand crosslinking agent MMC. Since TEGDMA produced oxidative stress, it probably acts indirectly on the cell cycle through reactive oxygen species, unless TEGDMA-DNA adducts are shown experimentally.
Eckhardt
Alexander
A
Department of Operative Dentistry and Periodontology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
Müller
Philipp
P
Hiller
Karl-Anton
KA
Krifka
Stephanie
S
Bolay
Carola
C
Spagnuolo
Gianrico
G
Schmalz
Gottfried
G
Schweikl
Helmut
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003188:Composite Resins / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity; D005434:Flow Cytometry; D008264:Macrophages / Q000187:drug effects; D008422:Materials Testing; D051379:Mice; D016685:Mitomycin / Q000633:toxicity; D018384:Oxidative Stress; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000633:toxicity*; D011109:Polymethacrylic Acids / Q000633:toxicity*
D000903:Antibiotics, Antineoplastic; D003188:Composite Resins; D010726:Phosphodiesterase Inhibitors; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D002110:Caffeine; D011092:Polyethylene Glycols; D016685:Mitomycin; D004317:Doxorubicin