Inhibition of parathyroid hormone-stimulated resorption in cultured fetal rat long bones by the main metabolites of ipriflavone

Among 1619 patients suspected of occupational contact dermatitis examined during the years 1990-1994, sensitivity to acrylates was diagnosed in 9 persons (4 dental technicians, 4 dentists, 1 textile printer). Ethyleneglycol dimethacrylate (5 positive patch tests), methyl methacrylate (4), 2-hydroxyethyl methacrylate (4) and triethyleneglycol dimethacrylate (4) were the most common sensitizers. Comparison of patch test results in dental technicians and dentists indicated that dentists were sensitive to a greater number of (meth)acrylate (acrylate and methacrylate) allergens and also to certain other allergens (metals and rubber additives). Dental technicians were sensitive almost exclusively to methacrylates, while the textile printer only to acrylates.     

Urocortin is not a significant regulator of intermittent electrofootshock-induced adrenocorticotropin secretion in the intact male rat

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.     

Monomethacrylate co-monomers for dental resins

Polymerisation shrinkage is widely recognised as a major drawback of resin based dental restoratives. Bis-GMA is often employed as the principal dimethacrylate monomer. Due to its high viscosity, Bis-GMA is normally mixed with large proportions of low viscosity glycol dimethacrylates. The purpose of this study was to determine whether the polymerisation shrinkage of Bis-GMA-based resins would be lower if alternative monomethacrylate co-monomers were used in place of conventional dimethacrylate co-monomers as viscosity modifiers. Conventional resins used were ethyleneglycol dimethacrylate and triethyleneglycol dimethacrylate; the alternative monofunctional co-monomers were tetrahydrofurfuryl methacrylate, hydroxypropyl methacrylate and isobornyl methacrylate. Model resins containing 54% mol/mol of co-monomer in Bis-GMA and 1% w/w of benzoyl peroxide as initiator were heat-cured at 70 degrees C for 8 h. Polymerisation shrinkage, degree of conversion and concentration of remaining methacrylate groups were calculated from density changes obtained gravimetrically. Other properties evaluated were Young's modulus, water uptake and viscosity of the monomer mixtures. The Bis-GMA-based resins exhibited lower shrinkage when mixed using the monomethacrylates rather than with conventional glycol dimethacrylates. Among the alternative co-monomers, tetrahydrofurfuryl methacrylate conferred the best balance of all measured properties.     

New method for the analysis of multiple positron emission tomography dynamic datasets: an example applied to the estimation of the cerebral metabolic rate of oxygen

Methacrylates are well-known contact sensitizers with increasing frequency of contact leading to occupational skin disease. Here, we developed an animal model to facilitate studies on the sensitizing capacities and cross-reactivity patterns between four clinically most important allergens: methacrylate (MMA), 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxypropyl methacrylate (2-HPMA) and ethyleneglycol dimethacrylate (EGDMA). Inbred guinea pigs were immunized by ic injections of 300 microliters of 1.0 M methacrylate solutions in Freund's complete adjuvant into both flanks, both ears, and the neck. After 14 days open skin tests were performed with 50% MMA, 2-HEMA, or 2-HPMA or 10% EGDMA solutions in 40% DMSO in ethanol. Cross-reactivities were investigated 14 days later by skin testing with all four methacrylates. Using this newly developed protocol, strongly positive skin tests for methacrylates could be induced in almost all guinea pigs (MMA 26/26, 2-HEMA 16/18, 2-HPMA 15/16 and EGDMA 11/11). Whereas EGDMA induced only weak or infrequent cross-reactivities, 2-HEMA sensitization led to strong cross-reactions to all other methacrylates. Both MMA and 2-HPMA induced strong cross-reactivity to EGDMA but only weak to moderate reactivities to the other methacrylates. The absence of strong cross-reactions with monomethacrylates in EGDMA (dimethacrylate)-sensitized animals may be explained by the predominance of highly EGDMA-specific T-cells in these animals. In contrast, sensitization with MMA, 2-HEMA, and 2-HPMA would lead to recruitment of T-cells cross-reactive to the other monomethacrylates, according to their molecular similarities. The strong skin hypersensitivities observed for EGDMA in these latter groups are ascribed to enzymatic degradation into monomethacrylate compounds, notably 2-HEMA, at a rate sufficient to elicit cognate effector T-cells. The results of this study offer new insights in the development of methacrylate hypersensitivities and common cross-sensitization patterns in clinical practice.     

Leaching and cytotoxicity of formaldehyde and methyl methacrylate from acrylic resin denture base materials

Acrylic resin dentures have the potential to elicit irritation, inflammation, and an allergic response of the oral mucosa. Studies of substances leachable from acrylic resins, their cytotoxicity to cultured cells, and means of reducing their leaching were systematically conducted. Under in vivo and in vitro conditions, formaldehyde and methyl methacrylate were significantly leached into human saliva and saliva-substitute buffer, especially from autopolymerized resins. Both leachable substances showed cytotoxic potentials in the range of their leaching concentrations. Formaldehyde was cytotoxic at lower concentrations than methyl methacrylate. Preleaching in water reduced subsequent leaching of both formaldehyde and methyl methacrylate, and the amount of reduction depended on an increase in the preleaching temperatures. Immersion of acrylic resin dentures in hot water (50 degrees C) before insertion is recommended, especially for autopolymerized resins used either for rebasing or as denture base materials, to minimize the risk of adverse reactions in patients who wear acrylic resin dentures.     

Effect of photoinitiator on degree of conversion of unfilled light-cured resin

In general, the concentrations of photosensitizer and reducing agent in light-cured dental polymers are fixed by manufacturers for a specific product. These concentrations vary from product to product and the effect of photoinitiator concentration on the final network structures is not clear. Accordingly, the influence of varying concentrations of camphorquinone (CQ) and amine reducing agent, 2-(N, N-dimethylamino)ethyl methacrylate (DMAEMA), on the degree of conversion (DC) of an unfilled light-cured resin was investigated. The resin consisted of 50 wt% triethyleneglycol dimethacrylate (TEGDMA) and 50 wt% 1,6-bis(methacryloxy-2-ethoxycarbonylamino)-2,4,4-trimeth ylhexane (UDMA) activated with varying concentrations of CQ (0.25-5 mol.%) and DMAEMA (0.125-5 mol.%). At low CQ concentrations, the DC measured by a Fourier Transform Infrared (FTIR) spectrometer increased rapidly with increasing concentration of DMAEMA and reached a plateau. At CQ concentrations of 0.5 mol.% and above, the plateau DC values were approximately 75-77%. On the basis of the systematic variations of CQ and DMAEMA, a contour representing the optimal combination of photoinitiator concentration from the standpoint of DC was established.     

Diffusion of monomers from bonding resin-resin composite combinations through dentine in vitro

OBJECTIVES: Previous work has demonstrated diffusion of the monomer triethylene glycol dimethacrylate (TEGDMA) from resin composite through dentine in vitro. The objective of the present work was to examine monomer diffusion from bonding resins and resin composites used in combination. METHODS: Occlusal cavities were prepared in tooth crowns and restored with bonding resin-resin composite combinations. Aqueous samples from the 'pulpal chamber' of each tooth were removed at timed intervals for analysis by reversed phase-high performance liquid chromatography and mass spectrometry. RESULTS: Bonding resins contributed to monomer diffusion. A TEDGMA-containing bonding resin used in combination with a TEGDMA-containing resin composite hastened and increased TEGDMA diffusion through dentine. A 2-hydroxyethyl methacrylate (HEMA)-containing bonding resin used in combination with a TEGDMA-containing resin composite reduced TEGDMA diffusion only slightly compared with the resin composite alone and added substantial diffusion of HEMA. CONCLUSION: The bonding resins tested contributed to monomer passage to the pulp space and did not prevent movement of monomer from resin composites to the pulp.     

Reinforcement of acrylic resins for provisional fixed restorations. Part I: Mechanical properties

Acrylic resins are commonly used in many dental applications; especially in the fabrication of provisional fixed partial dentures. Among noticed technical drawbacks associated with this material are unsatisfactory mechanical properties. Moreover, if acrylic resins are exposed to moist environment, water sorption results in further mechanical deterioration. In order to improve the mechanical properties, aluminum, magnesium, and zirconium oxide powders and pulverized E-glass particles were separately admixed with pre-polymerized acrylic resin beads prior to mixing with monomer liquid. Particle loading ratios were 1, 2 and 3 vol.% with respect to pre-polymerized beads. Poly(methyl methacrylate), poly(ethyl methacrylate) and poly(isobutyl methacrylate) were used as resin matrices. Furthermore, a metal primer agent was employed in order to form a strong interphase between admixed particles and polymer matrix phase. Samples were subjected to three-point transverse bending tests at a crosshead speed of 10 mm/min. It was concluded that (1) addition of particles generally increases the water sorbed by the composite resins systems, (2) however, two vol.% admixtures in a PMMA resin matrix showed significant improvements in the mechanical properties (p < 0.05), (3) among the oxide particles, zirconia exhibited the greatest improvements in modulus of elasticity, transverse strength, toughness and hardness, and (4) mechanical properties (transverse strength, 0.2% offset yield strength and modulus of elasticity) were linearly correlated to hardness numbers.     

Experiments of Applying the Rare-Earth Modifying Agents in New Dental Materials Preparation

Harmless rare-earth modifying agents were prepared by orthogonal experiments. A new resin material was synthesized with the qualities such as rigidity, rubbing abrasion, aging, luster and plasticity better than the dental resin materials in common used. It could be used as the substitutes for the applied resin teeth materials.     

Variability in cytotoxicity and fluoride release of resin-modified glass-ionomer cements

New-generation glass-ionomer cements contain resin to improve their restorative properties. These resin-modified glass-ionomer cements vary considerably in their chemistry, which could result in corresponding variability in their physical and biological properties. This study investigated the cytotoxicity and the fluoride release of two resin-modified glass ionomers, a conventional glass-ionomer cement, and a resin composite. Samples were prepared and extracted in distilled water for 1, 4, and 7 days; eluates were filtered and tested by means of 3T3 mouse fibroblasts. Cytotoxicity (MTT assay) values were low for all materials and extraction times, indicating minimal cytotoxicity of all materials (less than 30% inhibition). Cytotoxicity of one resin-modified glass ionomer was significantly higher than for the other materials (p < 0.001). One resin-modified glass ionomer and the conventional glass-ionomer cement released significantly more fluoride at each time interval (p < 0.001) than the other resin-modified glass-ionomer cement and the resin composite. Fluoride release and cytotoxicity were correlated (r2 = 0.60; p < 0.001), although the fluoride release does not account for the cytotoxicity observed. Cytotoxicity and fluoride release suggest that one hybrid behaved more like a conventional glass ionomer, and the other like a resin composite. These differences may have implications for material selection in specific clinical situations.     

Dual NF1-requiring effect of human neurotropic JC virus composite pentanucleotide repeat elements on early and late viral gene expression

OBJECTIVE: The purpose of this study was to prepare a light-cured adhesive applicable for orthodontics by mixing monomers and a polymerized reactive organic composite filler (prepolymerized trimethylolpropane trimethacrylate-filler, TMPT-filler). METHODS: The monomer component was a mixture of 3.0 wt% 2-hydroxy-3-(2-naphthoxy)propyl methacrylate (HNPM) in triethylene glycol dimethacrylate. This was applied to extracted bovine tooth enamel after acid etching with 65 wt% phosphoric acid for 30 s. After 24 h in 37 degrees C water, the tensile bond strength was measured, and the data were analyzed with Duncan's new multiple range test (p < 0.01 or 0.05). RESULTS: The tensile bonding strength to enamel etched with 65 wt% phosphoric acid was 13.1 +/- 0.5 MPa, and the thermal stability of the bond was excellent. SEM examination of the cross-sectioned specimens modified with HCl demineralization showed that when the diffusion time prior to light irradiation was only 1 min, a well-developed resin honeycomb-like structure was created in the enamel surface in the formulation containing HNPM. SIGNIFICANCE: Monomer impregnation beyond the etched enamel surface was important for resin-enamel bonding, increasing bonding strength and thermal stability. HNPM was effective in enhancing monomer diffusion and impregnation of the etched enamel surface.     

Relationship between composite matrix molecular structure and properties

The synthesis of three novel dimethacrylate esters for use as the monomer phase in dental composites was studied. The monomers were prepared by the reaction of glycidyl methacrylate with phthalic, isophthalic and terephthalic acids, respectively, and the reaction products were found to be mixtures of isomers. The monomers obtained from the reaction of phthalic and isophthalic acids were low-viscosity liquids and the relationship between viscosity and molecular structure was studied. The low viscosity of these di-hydroxyl containing monomers was shown to be due to intramolecular hydrogen bonding. This reduced monomer viscosity compared with BisGMA allowed a reduction in the quantity of diluent monomer triethyleneglycoldimethacrylate (TEGDMA) required to give standard viscosities of 1 and 2 Pas resulting in a modest decrease (ca. 10%) in polymerization shrinkage compared with that exhibited by BisGMA/TEGDMA solutions of equivalent viscosities. A number of properties relevant to the use of these as potential core monomers in dental composites were determined for both monomer and polymer systems.     

Memory training for remembering names: initial results in the healthy elderly

It has been known since the 1940s that nail polishes contain allergenic ingredients. The aim of this study was to clarify whether the nail polishes on the market today contain significant amounts of allergens, and what the solvents are. The following ingredients were determined: toluene, toluene sulfonamide formaldehyde resins, free formaldehyde, acrylates, methacrylates and certain organic solvents. The study comprised 20 brands and 42 samples. All the nail polishes analysed contained allergenic toluene sulfonamide formaldehyde resins (TSFR), in concentrations from 0.08 to 11.0%. The concentration of total formaldehyde varied from 0.02% to 0.5%. The more TSFR a nail polish contained, the higher was its formaldehyde content. Probably not only TSFR-allergic but also formaldehyde-allergic persons may get dermatitis from many of the nail polishes studied. The concentrations of acrylates and methacrylates were so small that they are of practical significance only to those previously sensitized to acrylates. Of the organic solvents, toluene was still widely used, whereas xylene was found in only 1 product. The nail polishes on the market today are not safe for all consumers. However, according to the regulations of the European Union, the packaging labeling of all cosmetic products must be supplied with a list of ingredients from the beginning of 1998. This will help the consumer to avoid allergenic products. A better alternative could, however, be to substitute the most allergenic ingredients with substances possessing minor allergy potency.     

Effect of dentine on release of TEGDMA from resin composite in vitro

Triethylene glycol dimethacrylate (TEGDMA) is a component of some resin composites which contributes to their cytotoxicity. The presence of dentine between resin composite and test cells reduces the cytotoxicity in vitro. To determine why dentine has this protective effect, the diffusion of TEGDMA from a composite resin through dentine to the pulp space was compared with release directly into aqueous solution in vitro. Both release rate and total cumulative release of TEGDMA for the two groups, at times up to 100 days, were determined using reversed-phase HPLC. Release rate directly into water was highest in the minutes immediately after immersion and declined thereafter. However, in the tooth model, using an equivalent mass and surface area of composite resin, no TEGDMA was detectable in the pulp space until 43 min after restoration placement. The rate of diffusion through dentine from that time until day 1 was less than 1% of the highest (initial) direct release rate. The rate declined thereafter. It is relevant, however, that by day 3 the total cumulative release of TEGDMA through dentine was 60% of the direct release. Dentine therefore appears to exert its protective effect principally by retarding or 'damping' the initial high release of TEGDMA to a substantial degree.     

2-(Dimethylamino)ethyl methacrylate based (co)polymers as gene transfer agents

Poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) is a water-soluble cationic polymer, which is able to bind to DNA by electrostatic interactions. At a polymer/plasmid ratio above 2 (w/w) positively charged complexes were formed with a size around 0.2 microm. The transfection efficiency of polymer/plasmid complexes was evaluated in cell culture (COS-7 and OVCAR-3 cells) using a pCMV-lacZ plasmid, encoding for beta-galactosidase, as a reporter gene. The optimal transfection efficiency was found at a PDMAEMA/plasmid ratio of 3-5 (w/w). Under these conditions 3-6% of the cells were actually transfected. Like other cationic polymers, PDMAEMA is slightly cytotoxic. This activity was partially masked by complexing the polymer with DNA. A pronounced effect of the molecular weight of the polymer on the transfection efficiency was observed. An increasing molecular weight resulted in an increasing number of transfected cells. Dynamic light scattering experiments showed that high molecular weight polymers (Mw>300 kDa) were able to condense DNA effectively (particle size 0.15-0.20 microm). In contrast, when plasmid was incubated with low molecular weight PDMAEMA, large complexes were formed (size 0.5-1.0 microm). Copolymers of DMAEMA with methyl methacrylate (MMA), ethoxytriethylene glycol methacrylate (triEGMA) or N-vinyl-pyrrolidone (NVP) also acted as transfection agents. A copolymer with 20 mol % of MMA showed a reduced transfection efficiency and a substantial increased cytotoxicity compared with a homopolymer of the same molecular weight. A copolymer with triEGMA (48 mol %) showed both a reduced transfection efficiency and a reduced cytotoxicity, whereas a copolymer with NVP (54 mol %) showed an increased transfection efficiency and a decreased cytotoxicity as compared to a DMAEMA homopolymer.     

Pharmacological activity of fluoxetine

This study introduces a new rapid-processing procedure for curing polymethyl methacrylate denture base resin in an automatically controlled pressure cooker. The cooker filled with water was inflated with 6 kgf/cm2 air pressure and heated to 120 degrees C (248 degrees F) and maintained for 10 minutes. No significant differences were found between the new pressure cooker method and the conventional method for surface hardness and porosity (p > 0.05). The pressure cooker significantly shortened polymerization time, and the polymerization is controlled automatically.     

Review of the biological response to a novel bone cement containing poly(ethyl methacrylate) and n-butyl methacrylate

This review describes work published independently elsewhere in which the biological reactions to poly(ethyl methacrylate) n-butyl methacrylate (PEMBMA) have been studied. This material has been compared throughout with conventional poly(methyl methacrylate) (PMMA). Butyl methacrylate monomer used in PEMBMA was slightly less toxic than methyl methacrylate monomer used in PMMA when injected intraperitoneally in mice. No differences in cardiorespiratory effects were found between n-butyl and methyl monomer infused intravenously into anaesthetized rabbits. The tissue reaction to the beaded polymers of poly(methyl methacrylate) and poly(ethyl methacrylate) implanted subcutaneously was identical. The surface appearance of the two materials differed significantly when viewed by scanning electron microscopy, showing a series of elevations resembling tightly packed spheres in the case of PMMA, but a smooth surface with only occasional smooth elevations in the case of PEMBMA. Intramuscular implantation showed more fibrous tissue and tissue damage in relation to PMMA cured in situ compared with PEMBMA and there was more bone necrosis and a thicker fibrous tissue layer adjacent to PMMA than PEMBMA when cured intraosseously.     

Artificial caries formation around fluoride-releasing restorations in roots

Secondary caries is one of the most important factors leading to replacement of dental restorations. This investigation assessed the capacity of fluoride-releasing restorative materials to resist caries in vitro when used in roots. Class 5 cavities were prepared in the buccal and lingual surfaces of 30 extracted premolars. The six materials used were: glass-ionomer cement (Fuji), glass-ionomer cement with silver particles added (Ketac-silver), fluoride-containing composite resin (Tetric), composite resin (Silux plus), fluoride-containing amalgam (Fluor-Alloy) and high-copper amalgam (Dispersalloy). After 5 weeks in an acid gel for caries-like lesion formation, the teeth were sectioned longitudinally and examined with polarized light. The results showed that repair with glass-ionomer materials of a carious lesion may be of great importance in the prevention of secondary caries around the restorations in roots.     

Marginal adaptation of resin-bonded light-cured glass ionomers in dentin cavities

PURPOSE: To investigate the marginal adaptation of resin-modified glass ionomer cements in dentin cavities placed with or without additional application of resin bonding systems. MATERIALS AND METHODS: Three resin-modified materials (Fuji II LC, Photac-Fil, Vitremer), one compomer (Dyract) and as reference an adhesively bonded resin composite system (Gluma CPS-Pekafill) were used. Flat peripheral dentin surfaces on human molar teeth were produced by wet grinding on SiC paper. Cylindrical cavities, 3.5 mm wide, were prepared in these dentin areas and restored with the individual materials. Sixty cavities were pretreated and restored as requested by the respective manufacturers. Following water storage of the specimens for 15 minutes or 24 hours, excess was gently removed by wet grinding for microscopic inspection of the marginal area. Additionally, in 30 cavities an experimental one-component adhesive resin system, a proprietary dimethacrylate and HEMA mixture dissolved in acetone, was combined with each of the restoratives for evaluation after 15-minutes water storage. Finally, in six cavities each, Dyract was combined with Prime and Bond 2.0, and Vitremer with Scotchbond Multi-Purpose Plus for assessment after 15 minutes. Maximum marginal gap widths (MGW) were measured. One-way ANOVA by ranks (Kruskal-Wallis-Test) followed by Wilcoxon's Two-Sample test were used to study the statistical difference of MGW among the treatment groups at a rejection level P = 0.05. RESULTS: Neither the conventionally placed material systems nor the restorations in combination with adhesives showed consistently gap-free margins after 15-minute water storage. After 24-hour storage with Vitremer 4 of the 6 restorations were gap-free, whereas with all other materials only perfect margins were registered. There was, however, no significant difference between the groups. Application of the experimental and/or the specific resin bonding agents had no effect on early MGW except for the Photac-Fil group, which was significantly reduced.     

Comparative cytotoxicity of 14 novel selenocysteine se-conjugates in rat renal proximal tubular cells

Recently, Se-substituted selenocysteine conjugates were proposed as potential prodrugs to target biologically active selenol compounds to tissues containing high activities of cysteine conjugate beta-lyases, such as the kidneys. However, several selenium compounds are known to be relatively toxic compounds. In the present study, the cytotoxicity of 14 selenocysteine Se-conjugates was determined in freshly isolated rat renal proximal tubular cells (RPTC). The results of this study show that four selenocysteine Se-conjugates with alkyl substituents (methyl, ethyl, n-propyl, and n-butyl) did not cause significant cytotoxicity to RPTC up to concentrations of 500 microM after 90 min of incubation. Also, no effect was observed on mitochondrial functioning as indicated by the unaffected mitochondrial membrane potential (delta psi). Se-(i-Propyl)-selenocysteine, however, appeared to be a cytotoxic compound, causing time- and dose-dependent cytotoxicity, and caused a decrease of delta psi in remaining viable cells. Aminooxyacetic acid (AOAA) provided significant protection against cell death of Se-(i-propyl)-selenocysteine, pointing to involvement of cysteine conjugate beta-lyase. AOAA, however, did not prevent the decrease of delta psi. Differentially substituted Se-(phenyl)-L-selenocysteine and Se-(benzyl)-L-selenocysteine conjugates appeared to be cytotoxic to RPTC at a concentration of 200 microM, as indicated by increased cell death and a decreased delta psi in remaining viable cells. Within the Se-benzyl-series, Se-(4-methoxybenzyl)-L-selenocysteine was the most toxic conjugate, whereas Se-(4-chlorophenyl)-L-selenocysteine was the most toxic conjugate of the Se-phenyl compounds. The selenocysteine Se-conjugates with nonsubstituted phenyl and benzyl substituents were nontoxic at 200 microM, but caused significant cell death at a concentration of 500 microM. Preincubation with AOAA, an inhibitor of cysteine conjugate beta-lyase, provided only partial protection against the cytotoxicity of Se-(phenyl)-L-selenocysteine (500 microM) and Se-(4-methoxybenzyl)-L-selenocysteine (200 microM). AOAA did not protect against cytotoxicity of the other conjugates, suggesting direct effects of these compounds or involvement of alternative routes of bioactivation. This study demonstrates that cytotoxicity of selenocysteine Se-conjugates is strongly dependent on the nature of the Se-bound substituent. The nontoxic Se-(alkyl)-Se-conjugates may be promising candidates for further evaluation for chemopreventive activities.