Objectives: Mammalian cell gene mutation assays are used for the analysis of genotoxic effects of medical devices used in dentistry. The hprt locus in Chinese hamster cells (V79 and CHO) and the tk locus in L5178Y mouse lymphoma cells are the most suitable selection markers for the isolation and quantification of induced gene mutations in routine testing. There is evidence that clastogenic substances are detected more precisely in the L5178Y/tk assay, and acrylates appear to induced genotoxicity through a clastogenic mechanism. Methods: We used L5178Y mouse lymphoma cells (without exogenous activation/inactivation) to analyze genotoxic effects caused by a serious of structurally-related comonomers of dental resin based materials. The induction of gene mutations at the tk locus and the formation of micronuclei by ethylene glycol dimethacrylate (EGDMA), diethylene glycol dimethacrylate (DEGDMA), triethylene glycol dimethacrylate (TEGDMA) and tetraethylene glycol dimethacrylate (TetEGDMA) were measured after a 4 hour exposure period. Results: All comonomers produced clear positive and dose related genotoxic responses in L5178Y cells with different potencies. The small EGDMA was the most reactive chemical in the L5178Y gene mutation assay. 1.0 mMol/l EGDMA induced about 1500 mutants/106 survivors, which is a mutant frequency (MF) 3.5-fold higher than control values. The activity of TetEGDMA (MF=1.6) was a bout 2-fold lower, and the effects of DEGDMA (MF=1.8) and TEGDMA (MF=2.09) were between these values. Similar, 1.0 mMol/l EGDMA induced numbers of micronuclei about 4-fold higher than control values, and all other chemicals were less effective. Conclusions: All difunctional methacrylate esters tested here are highly active in the L5178Y/tk test, and the effect in this gene mutation assay is structure related. Supported by a grant of the Deutsche Forschungsgemeinschaft (Schw 431/8-1)

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