Comparative study of the cytotoxicity of the nanosized and microsized tellurium powders on HeLa cells

To compare the cytotoxicity on HeLa cells induced by nanosized and microsized tellurium powders, HeLa cells were exposed to different concentrations of tellurium powders (0, 50, 100, 150 and 200 μg/mL) for 12 h. In this study, detection of a series of biomarkers, including reactive oxygen species (ROS), glutathione (GSH), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in addition to DNA and protein crosslink (DPC) and MTTassay, were conducted to evaluate the cytotoxicity. It is indicated that compared with the control group, there was no significant difference in the induced cytotoxicity at concentrations lower than 50 μg/mL for both nanosized and microsized tellurium powders. While there appears a significant difference in the induced cytotoxicity for nanosized tellurium powders when the concentration is higher than 100 μg/mL as well as for microsized tellurium powders when the concentration is higher than 200 μg/mL. Moreover, it is found that the cytotoxicity induced on HeLa cells exhibits a certain dose-effect relationship with the concentration of tellurium powders. A conclusion has been reached that the toxicity on HeLa cells can be induced by both nanosized and microsized tellurium powders, and the toxicity of the nanosized tellurium powders is significantly greater than the microsized one.     

Lipid Droplets in Schwann Cells During Tellurium Neuropathy Are Derived from Newly Synthesized Lipid

Exposure of weanling rats to a diet containing elemental tellurium results in a peripheral neuropathy characterized by segmental demyelination and minimal axonal degeneration. One of the earliest ultrastructural abnormalities in tellurium neuropathy is an increased number of cytoplasmic lipid droplets in myelinating Schwann cells. The pathogenesis of these lipid droplets was investigated using light and electron microscopic autoradiography. Nerve lipids were either "prelabeled" with [3H]acetate via in vivo intraneural injection 3 days before a 2-day exposure to tellurium, or "postlabeled" via in vivo intraneural injection or in vitro incubation with [3H]acetate following a 2-day exposure to tellurium. In the prelabeled nerves, myelin became heavily labeled, but the tellurium-induced cytoplasmic lipid droplets were rarely labeled. In the postlabeled nerves, the tellurium-induced cytoplasmic lipid droplets were the most heavily labeled structures within the nerve. These data indicate that the tellurium-induced lipid droplets in Schwann cells are derived from newly synthesized lipid rather than from the early breakdown and internalization of myelin lipids. The earliest biochemical abnormality observed in tellurium neuropathy is an inhibition of cholesterol synthesis at the squalene epoxidase step. This leads to an accumulation of squalene within the nerve. We conclude that the cytoplasmic lipid droplets in Schwann cells contain this accumulated lipid.     

Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls

Squalene monooxygenase is a flavin adenine dinucleotide-containing, microsomal enzyme that catalyzes the second step in the committed pathway for cholesterol biosynthesis. Feeding weanling rats a diet containing 1% elemental tellurium causes a transient, peripheral demyelination due to the disruption of cholesterol synthesis in Schwann cells secondary to inhibition of squalene monooxygenase. The tellurium species responsible for the inhibition is unknown, as is the mechanism of inhibition. To study the potential mechanisms of tellurium toxicity in humans, three likely in vivo metabolites of tellurium (tellurite, dimethyltellurium dichloride, and dimethyltelluride) were tested as inhibitors of purified human squalene monooxygenase. All three inhibitors reacted with the enzyme slowly and the resulting interaction was not freely reversible. The 50% inhibitory concentration for the methyltellurium compounds (approximately 100 nM) after a 30-min preincubation was 100-fold lower than that of tellurite, indicating a role for hydrophobicity in the enzyme-inhibitor interaction. The ability of glutathione and 2,3-dimercaptopropanol to prevent and reverse the inhibition indicated that the tellurium compounds were reacting with sulfhydryls on squalene monooxygenase, and the ability of phenylarsine oxide, which reacts specifically with vicinal sulfhydryls, to inhibit the enzyme indicated that these sulfhydryls are located proximal to one another on the enzyme. These results suggest that the unusual sensitivity of squalene monooxygenase to tellurium compounds is due to the binding of these compounds to vicinal cysteines, and that methylation of tellurium in vivo may enhance the toxicity of tellurium for this enzyme.     

Binding of tellurium to hepatocellular selenoproteins during incubation with inorganic tellurite: consequences for the activity of selenium-dependent glutathione peroxidase

The metallic group XVIa elements selenium and tellurium possess remarkably similar chemical properties. However, unlike selenium, tellurium is not an essential micronutrient and, indeed, induces both acute and chronic toxicity in a variety of species. Despite this, very little is known of the molecular mechanisms of toxicity of tellurium, particularly with respect to potential chemical interactions with selenium-containing components in the cell. In this work we describe a novel interaction of inorganic tellurite with hepatocellular selenoproteins, particularly with selenium-dependent glutathione peroxidase. The accumulation of (121Te)-tellurite into cultured primary rat liver hepatocytes was shown to be much more rapid than that of (75Se)-selenite on a molar basis. Neither the uptake of (121Te)-tellurite nor of (75Se)-selenite was affected by a large molar excess of the unlabelled counterpart, respectively. Interestingly, separation of the hepatocellular proteins on continuous pH denaturing gels demonstrated clear binding of radiolabelled tellurium to a number of protein bands, including one at 23 and one at 58 kDa, which corresponded to proteins readily labelled in cells treated with (75Se)-selenite. The binding of (121Te) to these proteins was insensitive to reduction with mercaptoethanol and not affected by pre-treatment of the cells with cycloheximide. When purified selenium-dependent glutathione peroxidase was treated directly with (121Te)-tellurite, the protein became labelled in an analogous manner to that achieved in intact cells. This was not affected by coincubation of the enzyme with (121Te)-tellurite and one or both of its substrates. Additionally, incubation of the peroxidase with tellurite effectively inhibited its ability to catalyse glutathione-dependent reduction of hydrogen peroxide. These data suggest that inorganic tellurite delivers tellurium to the intracellular milieu in a form capable of binding to some intracellular selenoproteins and at least in the case of glutathione peroxidase, cause inhibition of catalytic activity. The nature of the binding seems not to be due to the insertion of tellurocysteine into the protein and the insensitivity to reductive cleavage with mercaptoethanol seems to preclude the formation of stable telluro-selenides in the proteins. These data may offer alternative explanations for the established toxicity of tellurium via disruption of selenoprotein function, particularly by the induction of intracellular oxidative stress by the inhibition of Se-dependent glutathione peroxidase.     

X-ray diffraction studies on metal deposition in group D streptococci

Tucker, Fayne L. (University of Southern California, Los Angeles), John W. Thomas, Milo D. Appleman, Stewart H. Goodman, and Jerry Donohue. X-ray diffraction studies on metal deposition in group D streptococci. J. Bacteriol. 92:1311-1314. 1966.-Streptococcus faecalis N83 and S. faecium K6A reduced several compounds of Group VI elements to the elemental form, but reduced none of several compounds tested containing elements of other groups. The elemental tellurium deposited by S. faecium K6A was in general of a larger particle size than that deposited by S. faecalis N83 as judged from X-ray diffraction analysis. The particle size of the deposited tellurium was correlated with the blackness of the precipitate produced by cells growing in the presence of tellurite. A black and gray variation was observed in S. faecium K6A which was considered to be due to particle size, the amount of tellurium present, and the location of the deposited tellurium. The gray color of S. faecium K6A was not due to the presence of any oxidized tellurium products.     

Alterations in Gene Expression Associated with Primary Demyelination and Remyelination in the Peripheral Nervous System

Primary demyelination is an important component of a number of human diseases and toxic neuropathies. Animal models of primary demyelination are useful for isolating processes involved in myelin breakdown and remyelination because the complicating events associated with axonal degeneration and regeneration are not present. The tellurium neuropathy model has proven especially useful in this respect. Tellurium specifically blocks synthesis of cholesterol, a major component of PNS myelin. The resulting cholesterol deficit in myelin-producing Schwann cells rapidly leads to synchronous primary demyelination of the sciatic nerve, which is followed by rapid synchronous remyelination when tellurium exposure is discontinued. Known alterations in gene expression for myelin proteins and for other proteins involved in the sequence of events associated with demyelination and subsequent remyelination in the PNS are reviewed, and new data regarding gene expression changes during tellurium neuropathy are presented and discussed.     

Tellurium-Induced Neuropathy: Metabolic Alterations Associated with Demyelination and Remyelination in Rat Sciatic Nerve

Rats fed a diet containing 1.25% elemental tellurium initiated on postnatal day 20 undergo a transient neuropathy characterized by synchronous demyelination of peripheral nerves. In sciatic nerve, the extent of demyelination was maximal after 5 days of tellurium exposure; there was a loss of 25% of the myelin, as assayed by concentration of myelin-specific P0 protein. Tellurium-induced alterations in the metabolic capacity of Schwann cells were examined by measuring the synthesis of myelin lipids in vitro in isolated sciatic nerve segments. Exposure to tellurium resulted in an early marked decrease of approximately 50% in overall incorporation of [14C]acetate into lipids, with a preferential depression in synthesis of cerebrosides, cholesterol, and ethanolamine plasmalogens (components enriched in myelin). Most dramatically, within 1 day of initiation of tellurium exposure, there was a profound increase in [14C]acetate-derived radioactivity in squalene; 23% of incorporated label was in this intermediate of cholesterol biosynthesis, compared to less than 0.5% in controls. In association with the remyelinating phase seen after 5 days of tellurium exposure, synthesis of myelin components gradually returned to normal levels. After 30 days, metabolic and morphologic alterations were no longer apparent. We suggest that the sequence of metabolic events in sciatic nerve following tellurium treatment initially involves inhibition of the conversion of squalene to 2,3-epoxysqualene, and that this block in the cholesterol biosynthesis pathway results, either directly or indirectly, in the inhibition of the synthesis of myelin components and breakdown of myelin.     

Tellurite-induced damage of the erythrocyte membrane. Manifestations and mechanisms.

Chemical and biophysical mechanisms underlying the thiol-dependent lytic action of tellurite (and selenite) on human erythrocytes were investigated using native and GSH-depleted cells. Exposure of GSH-depleted cells to tellurite alone produces oxidative cross-linking of membrane thiols paralleled by a moderate membrane leakiness comparable in its extent to that induced by other SH-oxidizing agents (diamide, periodate). Exposure to tellurite in presence of endogenous or exogenous GSH produces marked leakiness which stems from the formation of aqueous leaks permeant to ions and nonelectrolytes and sensitive to inhibition by phloretin. Apparent pore radii, derived from exclusion limits for polar non-electrolytes, range from 0.3 to at least 1.3 nm. Leak size increases with increasing exposure time and concentration of the modifier. Leak formation is paralleled by membrane rigidification based on the cross-linking of spectrin. Thiol-dependent leak formation by tellurite in GSH-depleted cells can be sustained not only by exogenous GSH but also by other thiols. Progress of leak formation by tellurite/thiol can not be reliably quenched by procedures such as removal of tellurite from the medium, inhibition of anion transport via band-3 protein, washing of the cells or low temperature. The reaction can, however, be terminated, even in the presence of tellurite, by addition of N-ethylmaleimide, presumably due to the blockage of thiols or thiol-analogous tellurium compounds. N-ethylmaleimide even brings about a partial reversal of leakiness, suggesting the contribution of a reversible and an irreversible component of tellurite damage. Membrane perturbation by tellurite/thiol involves the formation of a membrane permeant tellurium species, possibly HTe-, which is likely to induce progressive damage of membrane proteins by a redox shuttle going along with a formation of elemental tellurium and its reduction by thiols.     

Pyridine-2,6-bis(thiocarboxylic acid) produced by Pseudomonas stutzeri KC reduces and precipitates selenium and tellurium oxyanions

The siderophore of Pseudomonas stutzeri KC, pyridine-2,6-bis(thiocarboxylic acid) (pdtc), is shown to detoxify selenium and tellurium oxyanions in bacterial cultures. A mechanism for pdtc's detoxification of tellurite and selenite is proposed. The mechanism is based upon determination using mass spectrometry and energy-dispersive X-ray spectrometry of the chemical structures of compounds formed during initial reactions of tellurite and selenite with pdtc. Selenite and tellurite are reduced by pdtc or its hydrolysis product H(2)S, forming zero-valent pdtc selenides and pdtc tellurides that precipitate from solution. These insoluble compounds then hydrolyze, releasing nanometer-sized particles of elemental selenium or tellurium. Electron microscopy studies showed both extracellular precipitation and internal deposition of these metalloids by bacterial cells. The precipitates formed with synthetic pdtc were similar to those formed in pdtc-producing cultures of P. stutzeri KC. Culture filtrates of P. stutzeri KC containing pdtc were also active in removing selenite and precipitating elemental selenium and tellurium. The pdtc-producing wild-type strain KC conferred higher tolerance against selenite and tellurite toxicity than a pdtc-negative mutant strain, CTN1. These observations support the hypothesis that pdtc not only functions as a siderophore but also is involved in an initial line of defense against toxicity from various metals and metalloids.     

Microbial processing of tellurium as a tool in biotechnology

Here, we overview the most recent advances in understanding the bacterial mechanisms that stay behind the reduction of tellurium oxyanions in both planktonic cells and biofilms. This is a topic of interest for basic and applied research because microorganisms are deeply involved in the transformation of metals and metalloids in the environment. In particular, the recent observation that toxic tellurite can be precipitated either inside or outside the cells being used as electron sink to support bacterial growth, opens new perspectives for both microbial physiologists and biotechnologists. As promising nanomaterials, tellurium based nanoparticles show unique electronic and optical properties due to quantum confinement effects to be used in the area of chemistry, electronics, medicine and environmental biotechnologies.     

Te(Ⅳ)胁迫对两种螺旋藻生长及抗氧化酶系统的影响

在钝顶螺旋藻(Spirulina platensis)和极大螺旋藻(Spirulina maximum)接种的第5天至第10天添加不同浓度的亚碲酸钠,研究Te(Ⅳ)胁迫对两种螺旋藻的生长、抗氧化活性系统和脂质过氧化作用的影响。结果表明,通过调节添加碲的时间,可以有效地调节碲胁迫强度,随着加碲时间依次后移,碲胁迫强度逐渐减小,螺旋藻的最终生物量递增。碲对螺旋藻的生物效应与碲胁迫强度有关,也与添加碲时藻所处的生长期有关。实验组Ⅲ(分别在第7、8、第9天三天添加碲)的碲胁迫强度并不是最低的,两种螺旋藻的最终生物量也不是最大,但MDA的含量却是最低的,表明该实验组的生长状态是最佳的。各种抗氧化酶(SOD、GPX、CAT、APX和POD)的活性变化情况较复杂。其中,在碲胁迫下,GPX的活性显著提高。       

Pyridine-2,6-Bis(Thiocarboxylic Acid) Produced by Pseudomonas stutzeri KC Reduces and Precipitates Selenium and Tellurium Oxyanions

The siderophore of Pseudomonas stutzeri KC, pyridine-2,6-bis(thiocarboxylic acid) (pdtc), is shown to detoxify selenium and tellurium oxyanions in bacterial cultures. A mechanism for pdtc's detoxification of tellurite and selenite is proposed. The mechanism is based upon determination using mass spectrometry and energy-dispersive X-ray spectrometry of the chemical structures of compounds formed during initial reactions of tellurite and selenite with pdtc. Selenite and tellurite are reduced by pdtc or its hydrolysis product H₂S, forming zero-valent pdtc selenides and pdtc tellurides that precipitate from solution. These insoluble compounds then hydrolyze, releasing nanometer-sized particles of elemental selenium or tellurium. Electron microscopy studies showed both extracellular precipitation and internal deposition of these metalloids by bacterial cells. The precipitates formed with synthetic pdtc were similar to those formed in pdtc-producing cultures of P. stutzeri KC. Culture filtrates of P. stutzeri KC containing pdtc were also active in removing selenite and precipitating elemental selenium and tellurium. The pdtc-producing wild-type strain KC conferred higher tolerance against selenite and tellurite toxicity than a pdtc-negative mutant strain, CTN1. These observations support the hypothesis that pdtc not only functions as a siderophore but also is involved in an initial line of defense against toxicity from various metals and metalloids.     

Plasmid-mediated resistance to tellurite: expressed and cryptic.

The ability of some bacteria to grow in the presence of high concentrations of tellurium compounds has been recognized for almost 100 years. Since then, interest in this phenomenon has generated a slow but steady trickle of literature. In the past few years, the use of modern techniques in molecular biology has led to a dramatic increase in our understanding of the genetics of several bacterial determinants for resistance to tellurium compounds. These determinants are frequently found to be encoded by plasmids which carry multiple antibiotic resistance determinants. Our understanding of the biochemistry of these systems remains limited. In this article, the history of the study of bacterial resistance to tellurium compounds is briefly reviewed. This is followed by an analysis of the recent developments in the study of plasmid-mediated resistance determinants. Finally, preliminary investigations on the possible mechanisms of bacterial resistance to tellurium compounds are presented.     

Dimethylselenide and Dimethyltelluride Formation by a Strain of Penicillium

A strain of Penicillium which produced dimethylselenide from inorganic selenium compounds was isolated from raw sewage. Sulfate and methionine enhanced growth of the fungus and its production of dimethylselenide in media containing selenite. In solutions containing selenate, methionine inhibited dimethylselenide formation while stimulating proliferation of the fungus. Dimethylselenide was also generated from inorganic selenide. Alkylation did not appear to be a significant mechanism of selenium detoxication by this organism. Dimethyltelluride was also produced by the organism from several tellurium compounds, but this product was synthesized only in the presence of both tellurium and selenium. The yields of dimethylselenide and dimethyltelluride varied with the relative concentrations of selenium and tellurium in the medium.     

Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase

The cDNA for human squalene monooxygenase, a key enzyme in the committed pathway for cholesterol biosynthesis, was amplified from a human liver cDNA library and cloned, and the protein was expressed in Escherichia coli and purified. Kinetic analysis of the purified enzyme revealed an apparent K(m) for squalene of 7.7 microM and an apparent k(cat) of 1.1 min(-1). For FAD the apparent K(m) is 0.3 microM, consistent with a loosely bound flavin. The apparent K(m) for NADPH-cytochrome P450 reductase, the requisite electron transfer partner, is 14 nM. The amount of reductase needed for maximal activity is about threefold less than the amount of squalene monooxygenase present in the assay; thus, electron transfer to the monooxygenase is not likely to be rate limiting. Previous reports have implicated inhibition of this enzyme as the cause of a peripheral demyelination seen in weanling rats fed a diet containing tellurium. As no data were available for humans, the ability of a number of tellurium and related elemental compounds to inhibit the recombinant human enzyme was examined. Tellurite, tellurium dioxide, selenite, and selenium dioxide were inhibitory; the tellurium compounds were more potent than the selenium compounds, as indicated by their IC(50) values (17 and 37 microM, respectively). Kinetic analysis of the inhibition by tellurite suggests multiple sites of interaction with the enzyme in a noncompetitive manner with respect to squalene.     

Role of Organotellurium Species in Tellurium Neuropathy

Exposure of weanling rats to a diet containing 1% elemental tellurium causes segmental demyelination of peripheral nerve, and an inhibition of squalene epoxidase. This inhibition is thought to be the mechanism of action leading to demyelination. Tellurite appears to be the active inhibitory species in a cell-free system but the active species in vivo is unknown. We examined potassium tellurite (K₂TeO₃) and three organotellurium compounds for their ability to inhibit squalene epoxidase in Schwann cell cultures and to induce demyelination in weanling rats. K₂TeO₃ had no effect on squalene epoxidase activity in cultured Schwann cells and caused no demyelination in vivo. All three organotellurium compounds caused inhibition of squalene epoxidase in vitro and caused demyelination in vivo. (CH₃)₂TeCl₂ was the most potent of these compounds and its neuropathy most resembled that caused by elemental tellurium. These data are consistent with the hypothesis that tellurium-induced demyelination is a result of squalene epoxidase inhibition and suggest that a dimethyltelluronium compound may be the neurotoxic species presented to Schwann cells in vivo.     

The Te-Assay: a black and white method for environmental sample pre-screening exploiting tellurite reduction

We present the tellurite bioassay (Te-Assay) as an alternative approach for quantification of cell viability. The Te-Assay was developed to pre-screen environmental samples for potential bacterial toxicants in which the reduction of tellurite to tellurium is used as a metabolic marker; black phenotype development only occurs in metabolically competent bacteria capable of reducing tellurite (TeO(3)(2-)) to elemental tellurium. The black and white phenotypes equate to nonsignificant or significant impediment of normal metabolic processes, thus permitting the rapid visual assessment of the relative toxicity of environmental samples. Bacterial inocula were exposed in 96-well plates to arrays of diluted analytes or environmental samples before addition of a tellurite to assess cell health/viability. Toxicity was quantified as the analyte concentration at which a 50% reduction in blackness occurred (IC(50)) compared to control wells containing no added analyte. No proprietary strains or reagents are required for Te-Assay, in which characterised strains or recent environmental isolates performed equally well. Strain selection was independent of tellurite-resistance provided that tellurite was reduced intracellularly by active non-growing cells.     

Sulfur,selenium and tellurium pseudopeptides: Synthesis and biological evaluation

A new series of sulfur, selenium and tellurium peptidomimetic compounds was prepared employing the Passerini and Ugi isocyanide based multicomponent reactions (IMCRs). These reactions were clearly superior to conventional methods traditionally used for organoselenium and organotellurium synthesis, such as classical nucleophilic substitution and coupling methods. From the biological point of view, these compounds are of considerable interest because of suspected anticancer and antimicrobial activities. While the sulfur and selenium containing compounds generally did not show either anticancer or antimicrobial activities, their tellurium based counterparts frequently exhibited antimicrobial activity and were also cytotoxic. Some of the compounds synthesized even showed selective activity against certain cancer cells in cell culture. These compounds induced a cell cycle delay in the G0/G1 phase. At closer inspection, the ER and the actin cytoskeleton appeared to be the primary cellular targets of these tellurium compounds, in line with some of our previous studies. As most of these peptidomimetic compounds also comply with Lipinski’s Rule of Five, they promise good bioavailability, which needs to be studied as part of future investigations.     

Tellurium-Induced Alterations in 3-Hydroxy-3-Methylglutaryl-CoA Reductase Gene Expression and Enzyme Activity: Differential Effects in Sciatic Nerve and Liver Suggest Tissue-Specific Regulation of Cholesterol Synthesis

The demyelination of peripheral nerves that results from exposure of developing rats to tellurium is due to inhibition of squalene epoxidase, a step in cholesterol biosynthesis. In sciatic nerve, cholesterol synthesis is greatly depressed, whereas in liver, some compensatory mechanism maintains normal levels of cholesterol synthesis. This tissue specificity was further explored by examining, in various tissues, gene expression and enzyme activity of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Exposure to tellurium resulted in pronounced increases in both message levels and enzyme activity in liver, the expected result consequent to up-regulation of this enzyme in response to decreasing levels of intracellular sterols. In contrast to liver, levels of mRNA and enzyme activity in sciatic nerve were both decreased during the tellurium-induced demyelinating period. The temporal pattern of changes in 3-hydroxy-3-methylglutaryl-CoA reductase message levels in sciatic nerve seen following exposure to tellurium was similar to the down-regulation seen for mRNA specific for PNS myelin proteins. Possible mechanisms for differential control of cholesterol biosynthesis in sciatic nerve and liver are discussed.     

Tellurite Specifically Affects Squalene Epoxidase: Investigations Examining the Mechanism of Tellurium-Induced Neuropathy

Abstract: A peripheral neuropathy characterized by a transient demyelinating/remyelinating sequence results when young rats are fed a tellurium-containing diet. The neuropathy occurs secondary to a systemic block in cholesterol synthesis. Squalene accumulation suggested the lesion was at the level of squalene epoxidase, a microsomal monooxygenase that uses NADPH cytochrome P450 reductase to receive its necessary reducing equivalents from NADPH. We have now demonstrated directly specificity for squalene epoxidase; our in vitro studies show that squalene epoxidase is inhibited 50% in the presence of 5 µ M tellurite, the presumptive in vivo active metabolite. Under these conditions, the activities of other monooxygenases, aniline hydroxylase and benzo( a )pyrene hydroxylase, were inhibited less than 5%. We also present data suggesting that tellurite inhibits squalene epoxidation by interacting with highly susceptible -SH groups present on this monooxygenase. In vivo studies of specificity were based on the compensatory response to feeding of tellurium. Following tellurium intoxication, there was up-regulation of squalene epoxidase activity both in liver (11-fold) and sciatic nerve (fivefold). This induction was a specific response, as demonstrated in liver by the lack of up-regulation following exposure to the nonspecific microsomal enzyme inducer, phenobarbital. As a control, we also measured the microsomal monooxygenase activities of aniline hydroxylase and benzo( a )pyrene hydroxylase. Although they were induced following phenobarbital exposure, activities of these monooxygenases were not affected following tellurium intoxication, providing further evidence of specificity of tellurium intoxication for squalene epoxidase.