title: 2-hydroxylethyl methacrylate (HEMA), a tooth restoration component, exerts its genotoxic effects in human gingival fibroblasts trough methacrylic acid, an immediate product of its degradation.
abstract: HEMA (2-hydroxyethyl methacrylate), a methacrylate commonly used in dentistry, was reported to induce genotoxic effects, but their mechanism is not fully understood. HEMA may be degraded by the oral cavity esterases or through mechanical stress following the chewing process. Methacrylic acid (MAA) is the primary product of HEMA degradation. In the present work we compared cytotoxic and genotoxic effects induced by HEMA and MAA in human gingival fibroblasts (HGFs). A 6-h exposure to HEMA or MAA induced a weak decrease in the viability of HGFs. Neither HEMA nor MAA induced strand breaks in the isolated plasmid DNA, but both compounds evoked DNA damage in HGFs, as evaluated by the alkaline comet assay. Oxidative modifications to the DNA bases were monitored by the DNA repair enzymes Endo III and Fpg. DNA damage induced by HEMA and MAA was not persistent and was removed during a 120 min repair incubation. Results from the neutral comet assay indicated that both compounds induced DNA double strand breaks (DSBs) and they were confirmed by the γ-H2AX assay. Both compounds induced apoptosis and perturbed the cell cycle. Therefore, methacrylic acid, a product of HEMA degradation, may be involved in its cytotoxic and genotoxic action.
authors: Department of Developmental Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland.
authors: Joanna
authors: J
authors: Szczepanska
authors: Tomasz
authors: T
authors: Poplawski
authors: Ewelina
authors: E
authors: Synowiec
authors: Elzbieta
authors: E
authors: Pawlowska
authors: Cezary J
authors: CJ
authors: Chojnacki
authors: Jan
authors: J
authors: Chojnacki
authors: Janusz
authors: J
authors: Blasiak
references: Mutat Res. 1997 Mar 12;383(2):167-75
references: 9088349
references: Biomaterials. 2008 Apr;29(10):1377-87
references: 18164055
references: J Biomed Mater Res B Appl Biomater. 2009 Feb;88(2):394-401
references: 18395826
references: Mutat Res. 2003 Feb 5;535(1):25-34
references: 12547280
references: Chin Med Sci J. 1994 Mar;9(1):1-7
references: 8086626
references: Dent Mater. 2008 Jan;24(1):134-40
references: 17920114
references: Biomaterials. 2005 Mar;26(7):745-53
references: 15350779
references: J Mater Sci Mater Med. 2006 Jun;17(6):495-500
references: 16691346
references: Scand J Dent Res. 1991 Jun;99(3):254-61
references: 1831287
references: Mutat Res. 1996 Jun 12;363(2):89-96
references: 8676929
references: Mutat Res. 2010 Feb;696(2):122-9
references: 20079459
references: J Adhes Dent. 2008 Feb;10(2):105-11
references: 18512507
references: DNA Repair (Amst). 2007 Jul 1;6(7):923-35
references: 17363343
references: Biomaterials. 2010 Nov;31(32):8164-71
references: 20673999
references: Cell Cycle. 2006 May;5(9):994-1000
references: 16687921
references: Toxicol Sci. 1998 May;43(1):19-27
references: 9629616
references: Dent Mater. 2009 Aug;25(8):1044-9
references: 19361853
references: Cytogenet Genome Res. 2010;128(1-3):28-36
references: 20407219
references: Biochem Biophys Res Commun. 2010 May 21;396(1):95-100
references: 20494118
references: J Dent. 2004 Mar;32(3):229-34
references: 15001288
references: Cancer Lett. 2005 Nov 18;229(2):171-9
references: 16129552
references: J Dent Res. 2008 Jul;87(7):661-5
references: 18573987
references: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12871-6
references: 14566050
references: Eur J Oral Sci. 2003 Jun;111(3):263-71
references: 12786959
references: Biomed Environ Sci. 1990 Sep;3(3):281-9
references: 2252547
references: Radiat Res. 2002 Oct;158(4):486-92
references: 12236816
references: J Biomed Mater Res. 2001 Dec 15;57(4):522-31
references: 11553882
references: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009 Dec;108(6):952-60
references: 19913728
references: J Endod. 2008 Oct;34(10):1191-7
references: 18793918
references: Crit Rev Oral Biol Med. 2001;12(2):136-51
references: 11345524
references: Mutat Res. 2008 Feb 29;650(2):115-22
references: 18178127
references: Dent Mater. 2007 Jun;23(6):688-95
references: 16890983
references: J Dent Res. 2006 Oct;85(10):870-7
references: 16998124
references: Scand J Dent Res. 1990 Jun;98(3):261-7
references: 2349453
references: Chem Biol Interact. 2009 Jun 15;180(1):69-78
references: 19428346
references: Mutat Res. 1998 Mar;407(2):169-76
references: 9637245
references: Am J Dent. 2009 Oct;22(5):295-8
references: 20225473
references: J Endod. 2008 Jun;34(6):684-8
references: 18498889
references: Exp Cell Res. 1988 Mar;175(1):184-91
references: 3345800
references: Cell Mol Life Sci. 2009 Mar;66(6):968-80
references: 19153659
references: Carcinogenesis. 1993 Sep;14(9):1733-5
references: 8403192
references: Toxicol In Vitro. 2010 Apr;24(3):854-62
references: 20005290
references: Chem Biol Interact. 2000 Dec 15;129(3):209-29
references: 11137062
references: Biomaterials. 2010 Mar;31(9):2508-16
references: 20022629
references: Biomaterials. 2009 Apr;30(11):2006-14
references: 19138796
references: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1991 Apr;13(2):144-7
references: 1831713
references: J Biomed Mater Res. 1987 Jan;21(1):11-23
references: 3558436
references: Proc Natl Acad Sci U S A. 2003 Apr 29;100(9):5057-62
references: 12679524
references: Biomaterials. 2010 Mar;31(8):2010-4
references: 20004467
references: Leukemia. 2010 Apr;24(4):679-86
references: 20130602
references: Biomaterials. 2005 Jul;26(19):4111-8
references: 15664638
references: Electrophoresis. 2009 Jun;30 Suppl 1:S181-7
references: 19517509
references: Mutat Res. 2009 Oct 2;669(1-2):169-76
references: 19559717
references: Mutat Res. 2000 Apr;462(2-3):121-8
references: 10767623
references: Biomaterials. 2010 Feb;31(5):818-23
references: 19833387
references: Mutat Res. 2007 Dec 1;634(1-2):156-62
references: 17719836
references: Environ Mol Mutagen. 2000;35(3):206-21
references: 10737956
references: Arch Oral Biol. 2004 Feb;49(2):125-31
references: 14693206
references: Curr Opin Genet Dev. 2009 Feb;19(1):82-91
references: 19233641
references: Dent Mater J. 2010 Jan;29(1):9-14
references: 20379006
references: J Appl Polym Sci Symp. 2008 Mar 15;107(6):3588-3597
references: 22919119
references: Biochem J. 1997 Jul 1;325 ( Pt 1):1-16
references: 9224623
references: J Biomed Mater Res B Appl Biomater. 2009 Oct;91(1):61-70
references: 19358261
references: Eur J Orthod. 2011 Feb;33(1):26-31
references: 20624754
references: Dent Mater. 2000 Jul;16(4):292-6
references: 10831785
references: Dent Mater. 2007 Jan;23(1):9-16
references: 16458349