Triethylene glycol dimethacrylate induces large deletions in the hprt geneof V79 cells

Acrylate esters are applied in industrial and consumer products often assoc iated with polymers and resins. The difunctional methacrylate, triethylene glycol dimethacrylate (TEGDMA), is also frequently included in dental compo site 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 mon omers in Salmonella typhimurium and V79 cells, Mutat. Res. 415 (1998) 119-1 30]. In the present study, TEGDMA caused a dose dependent increase of the n umber of micronuclei in V79 cells. Furthermore, the mutation spectra induce d 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 mutati ons were caused by point mutations. However, TEGDMA treated V79 cell cultur es exhibited different mutation spectra. Only one cell clone among a total of 25 contained all exon sequences of the hprt gene. Large DNA sequences we re deleted in 24 cell clones. Partial gene deletions occurred in four clone s from exon 5 through 9, and exon 1 was not amplified in one cell clone. Ex on sequences of the hprt gene were totally deleted in 19 HPRT-deficient clo nes. The induction of mostly large deletions in the genome of mammalian cel ls, like the mutation spectra induced by TEGDMA in V79 cells here, is proba bly typical for crosslinking agents, including anticancer drugs. Identical types of mutations including chromosomal aberrations and the formation of m icronuclei 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 a crylates and methacrylates. (C) 1999 Elsevier Science B.V. All rights reser ved.