Comparison of cytopathological changes induced by mercury chloride exposure in renal cell lines (VERO and BGM)

The response to mercury chloride was assessed in two cell lines of renal origin, determining the range of toxic concentrations by Neutral Red assay after 24-h of exposure. Morphological changes in the Buffalo Green Monkey (BGM) and VERO cell lines after exposure to subcytotoxic doses (0.045 and 0.038 mM, respectively) equivalent to EC10 (effective concentrations 10%) of mercury chloride were evaluated at the structural and ultrastructural level by optic, transmission and scanning microscopy. Using transmission electron microscopy, the most notable findings in treated cells were the presence of intracytoplasmic inclusion bodies and apoptotic bodies. Scanning microscopy pointed to a cell with a disrupted perinuclear region and a decreased number of surface microvilli. Similar alterations in both in vivo and in vitro experiments have been described by other authors. We conclude that BGM and VERO renal cell lines can be considered as useful tools for toxicological studies involving mercury chloride.     

Morphological alterations associated with HIV infection of CD4−/GalCer+ human intestinal epithelial cells

Summary The ultrastructural alterations induced by human immunodeficiency virus type 1 (HIV-1) in the human colon epithelial cell line HT-29 infected in vitro have been evaluated. These cells express high levels of galactosyl ceramide (GalCer), an alternative receptor for HIV-1 surface envelope glycoprotein gp120. Using immunolabelling for electron microscopy and immunofluorescence techniques, we detected the GalCer receptor in both the apical and basolateral membranes of differentiated HT-29 subclones. This nonpolar distribution is consistent with our previous observation that HIV infects both the apical and basolateral surfaces of epithelial cells in vitro. A transmission electron microscopy study demonstrated two major ultrastructural perturbations in the HIV-producing cells: (i) an unusual number of secretory granules; and (ii) the appearance of intracellular lumina with disorganized microvilli, indicating a defect in striated border assembly and differentiation. In addition to these morphological alterations, our study revealed the presence of fat vacuoles, concentric membranous bodies, tubuloreticular inclusions and giant mitochondria in the cytoplasm of HIV-infected cells. Taken together, these abnormalities could account for HIV-induced enteropathy, consisting of chronic diarrhea and malabsorption in the absence of enteric pathogens.     

A comparison of BGM and LLC-PK1 cells for the evaluation of nephrotoxicity

Nephrotoxicity is one of the most frequent effects observed after the use of medicine. Such situations have been tardily discovered because of existing methods to determine toxicity. The validation of sensitive, alternative methods for the early identification of toxic effects is as important as restrictions on the use of animals. In this light, the present study evaluated the effects of gentamicin on BGM and LLC-PK1 cells, using MTT and Neutral Red (NR). Although the LLC-PK1 cell line is used for toxicological studies, the BGM cell line is relatively new for this purpose. MTT (BGM: EC(50)?=?6.29 mM; LLC-PK1: EC(50)?=?8.01 mM) was found to be more sensitive than NR (EC(50) was greater than 10 mM for both cells). By using MTT, both cells demonstrated the involvement of mitochondria in a manner that was dose dependent, with an apoptotic process occurring at the concentrations of 1 and 3 mM and necrosis at concentrations above 4 mM. It could, therefore, be concluded that 1) BGM appears to be useful in the study of the mechanism of nephrotoxicity caused by gentamicin and 2) because of its sensitivity to MTT, in addition to its ease of manipulation, it is believed that the BGM cell line can also be used as an alternative method to evaluate nephrotoxicity.     

Morphologic and functional alterations induced by low doses of mercuric chloride in the kidney OK cell line: ultrastructural evidence for an apoptotic mechanism of damage

Mercury produces acute renal failure in experimental animal models, but the mechanism of tubular injury has not completely been clarified. There is an increased interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelial cells. However, detailed studies of morpho-functional alterations induced by mercuric chloride in kidney cell lines are scarce. This work characterizes these alterations in OK cell cultures. Morphological alterations were profiled using light microscopy, transmission electron microscopy, and confocal microscopy, as well as mitochondrial functional assays in the cells exposed to low concentrations of HgCl₂. At concentrations of 1 and 10 μM of HgCl₂ there were no morphological or ultrastructural alterations, but the mitochondrial function (MTT assay) and intracellular ATP content was increased, especially at longer incubation times (6 and 9 h). At 15 μM HgCl₂, both the mitochondrial activity and the endogenous ATP decreased significantly. At this concentration the OK cells rounded up, had increased number of cytoplasmic vacuoles, and detached from the cell monolayer. At 15 μM HgCl₂ ultrastructural changes were characterized by dispersion of the ribosomes, dilatation of the cisterns of the rough endoplasmic reticulum, increase of number of cytoplasmic vacuoles, chromatin condensation, invaginations of the nuclear envelope, presence of cytoplasmic inclusion bodies, and alterations in the size and morphology of mitochondria. At 15 μM HgCl₂ apoptotic signs included membrane blebbing, chromatin condensation, mitochondrial alterations, apoptotic bodies, and nuclear envelope rupture. Using confocal microscopy and the mitochondrial specific dye MitoTracker Red, it was possible to establish qualitative changes induced by mercury on the mitochondrial membrane potential after incubation of the cells for 6 and 9 h with 15 μM HgCl₂. This effect was not observed at short times (1 and 3 h) with this same concentration, neither with 1 and 10 μM HgCl₂ in all the studied times. Taken together, these findings indicate that low concentrations of HgCl₂ induce apoptosis by inhibiting mitochondrial function, and the OK cell line may be considered a useful tool for the study of programmed cell death involving mercurial species and other heavy metals.     

The effect of LSD on the surface of neuroepithelial cells

The neuroepithelial cells of 10 control chick embryos and of 22 exposed to lysergic acid diethylamide (LSD) (50 μg/ml) were examined in scanning electron microscopy (SEM). In specimens exposed to LSD, the cells are swollen and their surface loses its cytoplasmic projections. Labelling techniques applied in transmission electron microscopy (TEM) show that ruthenium red attaches to the surface of the neuroepithelial cells in the form of a continuous dark line in both controls and treated specimens. However, when cationized ferritin or lanthanum is used, the label appears in the form of a continuous line in the controls whereas it is discontinuous in specimens exposed to LSD. These observations suggest that LSD alters the components of the neuroepithelial cell surface in the young chick embryo.     

The Sensitivity of Lavage Analysis by Light and Analytical Electron Microscopy in Correlating the Types of Asbestos from a Known Exposure Setting

Lavage material was collected from 12 individuals whose work history included working in a cement manufacturing facility. The manufacturing processes of the facility included the use of crocidolite and chrysotile asbestos. Lavage material was prepared via digestion procedure and then analyzed for the presence of ferruginous bodies by light microscopy and for uncoated asbestos fibers by analytical transmission electron microscopy. A comparison was made as to the sensitivity between two analytical methods for linking a past exposure to a specific type of asbestos. The use of analytical transmission electron microscopy for identification of core material in the ferruginous bodies as well as for quantification of the uncoated asbestos fibers increased the sensitivity of the information obtained from lavage samples as necessary for confirming exposure in the past to specific types of asbestos.     

The sensitivity of lavage analysis by light and analytical electron microscopy in correlating the types of asbestos from a known exposure setting

Lavage material was collected from 12 individuals whose work history included working in a cement manufacturing facility. The manufacturing processes of the facility included the use of crocidolite and chrysotile asbestos. Lavage material was prepared via digestion procedure and then analyzed for the presence of ferruginous bodies by light microscopy and for uncoated asbestos fibers by analytical transmission electron microscopy. A comparison was made as to the sensitivity between two analytical methods for linking a past exposure to a specific type of asbestos. The use of analytical transmission electron microscopy for identification of core material in the ferruginous bodies as well as for quantification of the uncoated asbestos fibers increased the sensitivity of the information obtained from lavage samples as necessary for confirming exposure in the past to specific types of asbestos.     

Ultrastructural alterations in the liver and kidney of white sea bass, Lates calcarifer, in acute and subchronic cadmium exposure

Ultrastructural alterations in the liver and kidney of 3-month-old white sea bass, Latescalcarifer, after cadmium exposure were studied by transmission electron microscopy (TEM). One group of fish was exposed to a cadmium concentration of 10 mg/L (acute) for 96 h in a static system, and another group was exposed to cadmium concentrations of 0.8 and 3 mg/L cadmium (subchronic) for 3 months in a recirculation closed system. Ultrastructural alterations observed in the hepatocytes included mitochondrial condensation, swelling, and lysis. The rough endoplasmic reticulum (RER) showed dilation, fragmentation, and vesiculation. After subchronic exposure there were numerous large lipid droplets and abundant stored glycogen. Ultrastructural alterations observed in the proximal tubules of the kidney included nuclear degeneration, condensation, and massive swelling of the mitochondria; RER fragmentation and vesiculation. Disorganized brush borders and increased numbers of large hydropic vacuoles and lysosomes were also observed.     

Biological interactions of quantum dot nanoparticles in skin and in human epidermal keratinocytes

Quantum dots nanoparticles have novel optical properties for biomedical applications and electronics, but little is known about their skin permeability and interaction with cells. QD621 are nail-shaped nanoparticles that contain a cadmium/selenide core with a cadmium sulfide shell coated with polyethylene glycol (PEG) and are soluble in water. QD were topically applied to porcine skin flow-through diffusion cells to assess penetration at 1 microM, 2 microM and 10 microM for 24 h. QD were also studied in human epidermal keratinocytes (HEK) to determine cellular uptake, cytotoxicity and inflammatory potential. Confocal microscopy depicted the penetration of QD621 through the uppermost stratum corneum (SC) layers of the epidermis and fluorescence was found primarily in the SC and near hair follicles. QD were found in the intercellular lipid bilayers of the SC by transmission electron microscopy (TEM). Inductively coupled plasma-optical emission spectroscopy (ICP-OES) analysis for cadmium (Cd) and fluorescence for QD both did not detect Cd nor fluorescence signal in the perfusate at any time point or concentration. In HEK, viability decreased significantly (p<0.05) from 1.25 nM to 10 nM after 24 h and 48 h. There was a significant increase in IL-6 at 1.25 nM to 10 nM, while IL-8 increased from 2.5 nM to 10 nM after 24 h and 48 h. TEM of HEK treated with 10 nM of QD621 at 24 h depicted QD in cytoplasmic vacuoles and at the periphery of the cell membranes. These results indicate that porcine skin penetration of QD621 is minimal and limited primarily to the outer SC layers, yet if the skin were damaged allowing direct QD exposure to skin or keratinocytes, an inflammatory response could be initiated.     

Ultrastructural effects of cisplatin on the inner ear and lateral line system of zebrafish (Danio rerio) larvae

Zebrafish, Danio rerio, has been a prominent model vertebrate for the study of chemical toxicity and human disease. Zebrafish hair cells (HCs) show significant structural, functional and molecular similarities to the mammalian inner ear HCs. We examined the effects of cisplatin, an anti‐cancer drug, on HCs of the inner ear and on HCs and support cells (SCs) of neuromasts in zebrafish using transmission and scanning electron microscopy. Forty‐five zebrafish larvae, 12 days post‐fertilization, were assessed: 15 unexposed controls, 15 exposed to 10 µm cisplatin solution, and 15 exposed to 50 µm cisplatin solution. Hair cells in the cristae and maculae of the inner ear and of neuromasts were extremely sensitive to cisplatin. The drug was associated with vacuolization and the presence of myelinoid bodies in HC cytoplasm and with a condensation of the nuclear chromatin. The predominant pattern of injury was widespread degeneration of mitochondria, which appeared swollen and less electron‐dense with disorganized or reduced cristae. Severity of damage seemed to be concentration‐dependent, and the inner ear suffered more damage than the lateral line. Alterations similar to those in HCs were also observed in SCs of the neuromasts. Scanning electron microscopy showed loss of kinocilia in neuromasts of fish exposed to the higher concentration of cisplatin. Copyright © 2011 John Wiley & Sons, Ltd.     

Studies on uptake, sub-cellular trafficking and efflux of antisense oligodeoxynucleotides in glioma cells using self-assembling cationic lipoplexes as delivery systems

The cellular uptake of antisense oligodeoxynucleotides (ODNs) may be enhanced by the use of carriers such as cationic liposomes or lipoplexes, but little is known about the intracellular fate and subcellular trafficking of these systems in target cells. In this study, we report on the cellular uptake and biodistribution of ODNs in the presence and absence of optimised self-assembled cationic lipoplexes using the C6 glioma cell line as an in vitro model. Biotin or radiolabelled 15-mer phosphorothioate (PS) ODNs were synthesised and their cellular uptake and subcellular biodistribution characterised in the presence and absence of an optimised cationic lipoplex delivery system using studies ranging from cellular association, cellular efflux and transmission electron microscopy (TEM). Ultrastructural studies clearly showed PS ODNs in the absence of liposomal delivery to be sequestered within endosomal and lysosomal vesicular bodies indicative of endocytic uptake. ODNs were also visible, to a lesser extent, in the nucleus and cytoplasm. By employing DOSPA (2'-(1",2"-dioleoyloxypropyldimethyl-ammonium bromide)-N-ethyl-6-amidospermine tetra trifluoroacetic acid) and DOPE (dioleoylphosphatidylethanolamine) complex in a 3 : 1 ratio, as a delivery system for ODNs at a optimal lipid/DNA charge ratio of 1 : 1, the level of ODN cellular association was significantly increased by approximately 10-12 fold with a concomitant change in subcellular distribution of PS ODN. TEM studies indicated enhanced penetration of ODN within the cytosol and the cell nucleus with reduced presence in vesicular compartments. Efflux studies confirmed that cationic lipoplexes promoted entry of ODNs into 'deeper' cellular compartments, consistent with endosomal release. Optimised cationic lipoplexes improved cellular delivery of ODNs by enhancing cell association, uptake and by favourably modulating the intracellular trafficking and distribution of ODNs into non-vesicular compartments including the cytosol and nucleus.     

镉对雄性大鼠颌下腺颗粒曲管细胞损伤的光镜和电镜观察

目的研究镉对雄性大鼠颌下腺颗粒曲管(GCT)细胞的损伤。方法小剂量氯化镉(2mg/kg体质量)腹腔内注射后,观察光镜下GCT细胞的形态改变及计数各种细胞的数量变化;并用透射电镜动态观察GCT细胞的超微结构改变。结果①光镜下见镉注射后4h～60d,各组GCT细胞胞质染色变浅,分泌颗粒减少,无颗粒细胞数量显著减少,少颗粒细胞数量明显增多。②电镜下见镉注射后4h,GCT细胞胞质内髓样结构形成,部分线粒体肿胀,管周毛细血管内皮细胞微吞饮小泡增多;7d时,GCT细胞的损伤最为显著;30d时,细胞的超微结构损伤有所减轻;60d时,GCT细胞内线粒体仍有少数肿胀,毛细血管内皮细胞微吞饮小泡数量减少。结论镉对雄性大鼠GCT细胞的生物合成功能有损伤,其早期超微结构损伤与镉的直接作用有关。     

Inhalation of cadmium, lead or its mixture Effects on the bronchiolar structure and its relation with metal tissue concentrations

The human population in the industrialized world is constantly exposed to chemical mixtures of pollutants such as metals; information about the consequences of the interactions of these compounds on health is scarce. The current study examines the effects of the inhalation of lead (Pb), cadmium (Cd) and Pb-Cd mixture in mice models analyzing the metal concentrations in lung, and the morphological modifications in the bronchiolar epithelium identified by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) after 4 weeks of inhalation. Our results showed that metal concentrations in lung were higher compared to controls; however, Pb concentrations drastically decrease with the mixture. This reduction was also observed in the inhalation chamber. These data correlate with the morphological alterations observed, which consisted of flattened and decreased number of nonciliated bronchiolar cells (NCBC), bald ciliated cells and bundles of NCBC. These modifications were mainly given by Cd, alone or in combination with Pb. The clusters formed by NCBC cells suggest cell proliferation which probably means that after metal inhalation, the cells enhance their proliferative capacity in order to repopulate the bronchiolar wall.     

Changes in muntjac fibroblasts associated with the acquisition of cadmium resistance

A series of cell lines with different levels of resistance to continuous cadmium exposure has been developed from an immortal but non-transformed muntjac fibroblast cell line. Concentrations accepted in their culture medium range from 0.1 M for the cadmium sensitive parent line to 5 M for the intermediate cadmium-tolerant line, to 5, 10, 20 and 50 M for the four cadmium-resistant lines. The present paper follows the morphological changes which accompanied the development of resistance through a 20-month pre-resistance period, a relatively abrupt 6-week transitional period and a 3-year post-resistance period, during which time levels of cadmium resistance were increased. Initial changes which led to the cadmium-tolerant CR5 cell line included (i) increased efficiency in autophagocytosing damaged cell components and in ridding the cell of residual waste materials, (ii) a reduction in fluid filled vacuoles and (iii) improved recycling and/or replacement of cadmium-damaged cell membrane. With the advent of cadmium resistance the intracellular damage necessitating these activities disappeared, yet the series of changes which occurred included a massive build-up of Golgi and the appearance of a trans-Golgi tubular network in addition to cytoskeletal and membrane changes. Though metallothionein levels are greater in the cadmium-resistant variants, their increase appears inadequate on their own to account for the high levels of resistance. The post-resistance changes which accompanied each step-up in cadmium resistance included further membrane and glycocalyx changes, in addition to continued increases in Golgi bodies and tubular network. This paper details the morphological changes which occurred throughout the 5-year period, tests the direct dependence of each on the presence of cadmium and examines their possible contribution to a cadmium protective mechanism.     

Effects of long-term cadmium exposure on the testis of rabbits: ultrastructural study

Six male rabbits received for 9 months drinking water containing 20 micrograms/ml of cadmium (Cd). At the end of the treatment, the Cd contents of kidney and testis were 175 +/- 34 and 0.8 +/- 0.2 micrograms/g wet weight, respectively. Ultrastructural examination by transmission electron microscopy (EM) showed that, in the Sertoli cells, the size of the lysosomes was increased; spermatogenetic cells, vessels and Leydig cells showed no significant alterations. Observations with both transmission and scanning EM did not evidence changes in the blood-testis barrier, but our results do not exclude that male fertility may be affected by chronic exposure to cadmium.     

Impact of acute cadmium exposure on the trunk lateral line neuromasts and consequences on the "C-start" response behaviour of the sea bass (Dicentrarchus labrax L.; Teleostei, Moronidae)

Behavioural responses of sea bass Dicentrarchus labrax were investigated after exposure to cadmium ions in laboratory-controlled conditions. The aim of this study was to discover whether environmental exposure to cadmium ions inactivates fish lateral line system neuromasts, and to determine the behavioural consequences of such a sensory blockage. For this, fish escape behaviour in response to an artificial water jet was recorded using a 25-frames s(-1) analog video camera before and after cadmium exposure. Experimental set up was tested with fish whose lateral line system was artificially inactivated by antibiotics (gentamicin and streptomycin). Histological analyses with scanning electron microscopy showed antibiotic treatment destroyed lateral line system neuromasts. In addition, these fish did not respond to stimulations provoked by the water jet after antibiotic treatment. Fish escape behaviour was then recorded before and after cadmium exposure at two different concentrations. When fish were exposed to the first concentration of cadmium tested (0.5 microg l(-1), which represents the maximal cadmium concentration encountered in contaminated estuaries), no alteration in neuromast tissue was observed. In addition, before cadmium exposure, fish responded positively in 98.41 +/- 4.95% of lateral line system stimulations (escape behaviour in response to the water jet). After cadmium exposure, no behavioural modification could be detected: the fish responded positively in 95.16 +/- 9.79% of stimulations (chi(2) = 2.464, p = 0.116). In contrast, the high cadmium concentration used (5 microg l(-1), which represents 10 times the concentration occurring in highly polluted estuarine areas) involved severe neuromast tissue damage. Just after such cadmium exposure, fish showed only 41.67 +/- 35.36% of positive responses to their lateral line system stimulations, while they responded positively in 95.93 +/- 9.10% of stimulations under control conditions (chi(2) = 24.562, p < 0.0001). Their lateral line system neuromasts seemed to regenerate about 1 month after cadmium exposure. Associated with this regeneration, from the 21st day after cadmium exposure, their escape behaviour had recovered and was not significantly different from that recorded under control conditions (86.74 +/- 20.82%, chi(2) = 2.876, p = 0.090). This study shows that although 5 microg l(-1) cadmium is able to damage lateral line system neuromasts and causes fish behavioural alterations, fish exposed to 0.5 microg l(-1) cadmium displayed neither tissue neuromast nor behavioural modification.     

水溶性紫杉醇衍生物PLT抗肿瘤活性的实验研究

目的观察水溶性紫杉醇衍生物(Peg-Leu-Taxol,PLT)的抗肿瘤活性及机制.方法以MTT还原法检测PLT对肿瘤细胞生长的抑制作用,以相差显微镜和荧光显微镜观察细胞形态学改变,免疫组化方法检测细胞生长相关基因p21wafl表达.结果PLT能明显抑制乳腺癌(MCF-7)、非小细胞肺癌(PG-49)和红白血病(K562)细胞的生长.细胞形态呈凋亡特征性改变,细胞皱缩,核染色质凝缩、碎裂、亮珠状浓染.细胞p21wafl蛋白表达显著增高.结论PLT具有明显的抗肿瘤活性,其诱导肿瘤细胞凋亡与p21wafl基因表达上调有关.     

Aptamer Tethered Bio-Responsive Mesoporous Silica Nanoparticles for Efficient Targeted Delivery of Paclitaxel to Treat Ovarian Cancer Cells

Ovarian cancer is the leading cause of cancer deaths in female patients. The current therapeutics in ovarian cancer are limited and inefficient in curing the disease. To tackle this, we have synthesized tetrasulfide derivative of silica doped, biodegradable, glutathione-responsive targeted mesoporous silica nanoparticles modified with heterobifunctional polyethylene glycol as a linker and mucin-1 aptamer for triggered paclitaxel delivery to the ovarian cancer cells. Degradable mesoporous silica nanoparticles were synthesized by a modified sol-gel method with tetraethyl orthosilicate and Bis (triethoxysilylpropyl) tetrasulfide. The degradable mesoporous silica nanoparticles were characterized by dynamic light scattering, Fourier-transform infrared spectroscopy, Scanning electron microscopy and Transmission electron microscopy. The degradable mesoporous silica nanoparticles had good paclitaxel encapsulation efficiency and glutathione-responsive paclitaxel release ability. The glutathione utilization assay and visual destruction observed within 10 days in transmission electron microscopy images confirmed the degradation of the mesoporous silica nanoparticles in the tumor cell environment. The targeted degradable mesoporous silica nanoparticles were efficiently taken up by ovarian cancer cell lines OVACAR-3 and PA-1. The cytotoxicity of bare mesoporous silica nanoparticles evaluated on NIH-3T3 cell line showed good biocompatibility (>90% cell viability). Significant toxicity on OVACAR-3 (IC₅₀ 25.66 nM) and PA-1 (IC₅₀ 42.93 nM) cell lines was observed when treated with paclitaxel-loaded targeted degradable mesoporous silica nanoparticles. Results of this study demonstrated that mucin-1 targeted, glutathione-responsive mesoporous silica nanoparticles loaded with paclitaxel had a significant antitumor effect on ovarian cancer cells. All these findings demonstrated that developed nano-formulation could be suitable for ovarian cancer treatment.     

直茎紫堇对细粒棘球蚴作用的电镜观察

感染细粒棘球蚴病的小白鼠经直茎紫堇总碱治疗后,其体内棘球蚴生发膜的超微结构有明显变化,主要表现为生发膜皮层细胞微毛消失,细胞器排列紊乱,胞浆中微管局限性扩张、破裂,溶酶体增多,高尔基复合体数目减少,线粒体肿胀和退行性变。棘球蚴生发膜外表面和内表面出现许多陷窝,如同“溃疡”外观。初步结果表明直茎紫堇总碱对细粒棘球蚴有广泛的细胞内效应。     

Intracellular behaviour of uranium(VI) on renal epithelial cell in culture (LLC-PK1): influence of uranium speciation

The main objective of this work was to assess the potentiality of in vitro models to study and understand the uranium-induced cytotoxicity on renal cells. Cytotoxicity and morphological studies were performed in a tubular proximal original established cell line (LLC-PK1 cell line). Dose-dependent cytotoxicity response was obtained with the uranium bicarbonate complex. In vitro experiments revealed a toxicity of uranium-bicarbonate complexes after a 24-h exposition and for concentrations ranging from 7 x 10(-4) M to 10(-3) M. In contrast, a lack of cytotoxicity of uranium(VI) citrate complexes studied using the same experimental conditions was noticed. Furthermore, electron transmission microscopy and X-ray microanalysis studies, after exposition of LLC-PK1 cells to the uranium-bicarbonate system ([U] = 8 x 10(-4) M) revealed that uranium entered into the cells and it was precipitated within the cytoplasmic compartment as uranyl phosphate needles. Similar morphological studies conducted with citrate complexes did not show any intake of uranium by LLC-PK1 cells. Experiments conducted in phosphate free culture medium showed that uranium was incorporated as a soluble material and that the association of the metal with phosphate ions occurred in the cytoplasmic compartment of LLC-PK1 cells.