The effect of triethylene glycol dimethacrylate on the cell cycle of mammalian cells.
The induction of DNA damage by a genotoxic agent is a signal leading to cell cycle delay, and thereby enables and induces DNA repair prior to cell cycle progression. Triethylene glycol dimethacrylate (TEGDMA), a monomer of dental resinous materials, caused mutagenic effects in mammalian cells probably as a consequence of DNA damage. Therefore, we hypothesized that TEGDMA will induce a cell cycle delay in mammalian cells. Here, cell lines deficient and proficient of a functional p53 tumor suppressor protein were used to study the effects of TEGDMA on the various phases of the cell cycle. V79 Chinese hamster lung fibroblasts (p53 deficient), N1 human skin fibroblasts (p53 proficient), and primary human pulp fibroblasts (p53 proficient) were exposed to increasing TEGDMA concentrations (0-3 mmol/l). Cell survival and vitality were determined after a 24-h exposure period and a 24-h recovery period, and the distribution of cells between the phases of the cell cycle in untreated and TEGDMA-treated cultures was analyzed by flow cytometry. The majority of the TEGDMA-treated V79 cells accumulated in G2 phase. In contrast, about 30% of human N1 fibroblasts were reversibly blocked in G1 phase by 0.5-3.0 mmol/l TEGDMA. The fraction of G2-phase cells was increased only by high TEGDMA concentrations. The percentage of human pulp cells in G1 phase increased very slightly with 1 mmol/l TEGDMA, but cell numbers in G1 phase were reduced by 10-20% by 1.5-3 mmol/l TEGDMA. The percentage of pulp cells in G2 phase increased about 2-fold without any obvious effect of a 24-h recovery period. Therefore, TEGDMA caused cell cycle delays through p53-dependent and independent pathways in the various cell lines. From these results, we conclude that TEGDMA may influence physiological processes like cell growth and differentiation of human pulp cells in vivo.
Schweikl
Helmut
H
Department of Operative Dentistry and Periodontology, University of Regensburg, D-93042 Regensburg, Germany. helmut.schweikl@klinik.uni-regensburg.de
Altmannberger
Inge
I
Hanser
Nico
N
Hiller
Karl-Anton
KA
Bolay
Carola
C
Brockhoff
Gero
G
Spagnuolo
Gianrico
G
Galler
Kerstin
K
Schmalz
Gottfried
G
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D003764:Dental Materials / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008422:Materials Testing; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011109:Polymethacrylic Acids / Q000009:adverse effects*
D003764:Dental Materials; D011109:Polymethacrylic Acids; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D004247:DNA