Triethylene glycol dimethacrylate induces large deletions in the hprt gene of V79 cells

被引:89
作者
Schweikl, H [1 ]
Schmalz, G [1 ]
机构
[1] Univ Regensburg, Dept Operat Dent & Periodontol, D-93042 Regensburg, Germany
关键词
mutagenicity; acrylate ester; triethylene glycol dimethacrylate; dental material; DNA deletion; V79; cell;
D O I
10.1016/S1383-5718(98)00164-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Acrylate esters are applied in industrial and consumer products often associated with polymers and resins. The difunctional methacrylate, triethylene glycol dimethacrylate (TEGDMA), is also frequently included in dental composite materials. Recently, mutagenicity testing of the compound revealed the induction of gene mutations at the hprt locus in V79 cell [H. Schweikl, G. Schmalz, K. Rackebrandt, The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells, Mutat. Res. 415 (1998) 119-130]. In the present study, TEGDMA caused a dose dependent increase of the number of micronuclei in V79 cells. Furthermore, the mutation spectra induced in exon sequences of the hprt gene in HPRT-deficient V79 cell clones were analyzed by the polymerase chain reaction (PCR). No DNA sequence deletions were observed in spontaneously occurring HPRT-deficient cell clones at the molecular level after PCR analysis, indicating that all spontaneous mutations were caused by point mutations. However, TEGDMA treated V79 cell cultures exhibited different mutation spectra. Only one cell clone among a total of 25 contained all exon sequences of the hprt gene. Large DNA sequences were deleted in 24 cell clones. Partial gene deletions occurred in four clones from exon 5 through 9, and exon 1 was not amplified in one cell clone. Exon sequences of the hprt gene were totally deleted in 19 HPRT-deficient clones. The induction of mostly large deletions in the genome of mammalian cells, like the mutation spectra induced by TEGDMA in V79 cells here, is probably typical for crosslinking agents, including anticancer drugs. Identical types of mutations including chromosomal aberrations and the formation of micronuclei in vitro were observed for acrylates and methacrylates tested so far in various mutation assays. Therefore, we conclude by analogy that the induction of large DNA sequence deletions as shown here with the reactive dimethacrylate, triethylene glycol dimethacrylate, is probably common for acrylates and methacrylates. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:71 / 78
页数:8
相关论文
共 29 条
[1]   HEXAMETHYLMELAMINE IS A POTENT INDUCER OF DELETIONS IN MALE GERM-CELLS OF DROSOPHILA-MELANOGASTER [J].
AGUIRREZABALAGA, I ;
NIVARD, MJM ;
COMENDADOR, MA ;
VOGEL, EW .
CARCINOGENESIS, 1995, 16 (11) :2679-2683
[2]   REVIEW OF THE TOXICITY OF MULTIFUNCTIONAL ACRYLATES [J].
ANDREWS, LS ;
CLARY, JJ .
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH, 1986, 19 (02) :149-164
[3]   MUTAGENESIS BY CHEMICAL-AGENTS IN V79 CHINESE-HAMSTER CELLS - A REVIEW AND ANALYSIS OF THE LITERATURE - A REPORT OF THE GENE-TOX PROGRAM [J].
BRADLEY, MO ;
BHUYAN, B ;
FRANCIS, MC ;
LANGENBACH, R ;
PETERSON, A ;
HUBERMAN, E .
MUTATION RESEARCH, 1981, 87 (02) :81-142
[4]   Large deletions induced in the white gene of Drosophila melanogaster by the antitumoral drug cis-dichlorodiammineplatinum(II): Influence of non-homologous recombination [J].
Cizeau, J ;
Decoville, M ;
Leng, M ;
Locker, D .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1996, 356 (02) :197-202
[5]   MOLECULAR ANALYSIS OF MUTATIONS AT THE TK LOCUS OF L5178Y MOUSE-LYMPHOMA CELLS INDUCED BY ETHYL METHANESULFONATE AND MITOMYCIN-C [J].
DAVIES, MJ ;
PHILLIPS, BJ ;
RUMSBY, PC .
MUTATION RESEARCH, 1993, 290 (02) :145-153
[6]   ANALYSIS OF THE GENOTOXICITY OF 9 ACRYLATE METHACRYLATE COMPOUNDS IN L5178Y MOUSE LYMPHOMA-CELLS [J].
DEARFIELD, KL ;
MILLIS, CS ;
HARRINGTONBROCK, K ;
DOERR, CL ;
MOORE, MM .
MUTAGENESIS, 1989, 4 (05) :381-393
[7]   ACRYLAMIDE - ITS METABOLISM, DEVELOPMENTAL AND REPRODUCTIVE EFFECTS, GENOTOXICITY, AND CARCINOGENICITY [J].
DEARFIELD, KL ;
ABERNATHY, CO ;
OTTLEY, MS ;
BRANTNER, JH ;
HAYES, PF .
MUTATION RESEARCH, 1988, 195 (01) :45-77
[8]   GENOTOXICITY IN MOUSE LYMPHOMA-CELLS OF CHEMICALS CAPABLE OF MICHAEL ADDITION [J].
DEARFIELD, KL ;
HARRINGTONBROCK, K ;
DOERR, CL ;
RABINOWITZ, JR ;
MOORE, MM .
MUTAGENESIS, 1991, 6 (06) :519-525
[9]   MICRONUCLEUS, CHROMOSOME ABERRATION, AND SMALL-COLONY TK MUTANT ANALYSIS TO QUANTITATE CHROMOSOMAL DAMAGE IN L5178Y MOUSE LYMPHOMA-CELLS [J].
DOERR, CL ;
HARRINGTONBROCK, K ;
MOORE, MM .
MUTATION RESEARCH, 1989, 222 (03) :191-203
[10]   ANALYSIS OF X-RAY-INDUCED HPRT MUTATIONS IN CHO CELLS - INSERTION AND DELETIONS [J].
FUSCOE, JC ;
ZIMMERMAN, LJ ;
FEKETE, A ;
SETZER, RW ;
ROSSITER, BJF .
MUTATION RESEARCH, 1992, 269 (02) :171-183