Hanna Tähti

Hanna Tähti
Tampere University | UTA · Medical Faculty

Ph.D., Professor emerita

About

97
Publications
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Introduction
Alternative methods in toxicology Cell and tissue based research models in the use of toxicological research

Publications

Publications (97)
Article
European Consensus Platform for Alternatives (ecopa) and Scandinavian Society for Cell Toxicology (SSCT) hosted the joint ecopa‐SSCT workshop “Up‐to‐date in vitro approaches in regulatory risk assessment and disease modeling” in Helsinki, 14‐16 June 2017. The workshop consisted of three scientific sessions and poster sessions, all together 28 oral...
Article
Full-text available
The extent of information needed and the tests required for the assessment of carcinogenic and genotoxic potencies of chemical substances significantly vary among different regulatory requirements. In the hazard and risks assessments in vitro and in vivo genotoxicity studies are used and they are often followed by rodent 2-year bioassay(s). The in...
Article
There is an urgent need to develop predictive test methods better than animal experiments for assessing the safety of chemical substances to man. According to today's vision this is achieved by using human cell based tissue and organ models. In the new testing strategy the toxic effects are assessed by the changes in the critical parameters of the...
Article
The Björn Ekwall Memorial Foundation (BEMF) was initiated by the Scandinavian Society for Cell Toxicology in 2001, to honour the memory of Dr Björn Ekwall (1940-2000) and to establish a prize, the Björn Ekwall Memorial Award. The prize is awarded to scientists who have significantly contributed to the field of cell toxicology, and whose work is con...
Article
Full-text available
The 7th amendment to the EU Cosmetics Directive prohibits to put animal-tested cosmetics on the market in Europe after 2013. In that context, the European Commission invited stakeholder bodies (industry, non-governmental organisations, EU Member States, and the Commission's Scientific Committee on Consumer Safety) to identify scientific experts in...
Article
The combination of an in vitro BBB model (4d/24w) with a neuronal cell line (SH-SY5Y) provides a convenient approach to explore the importance of BBB permeability in neurotoxicity assessment of compounds. The toxicity of 16 compounds on SH-SY5Y cells was evaluated after 24h incubation with each compound and compared to their toxicity on SH-SY5Y aft...
Article
In-vitro models that maintain complex transport mechanisms and structural properties associated with the blood-brain barrier in vivo would be useful in drug permeability and neurotoxicological studies. To evaluate the suitability of a human retinal pigment epithelial cell line for a blood-brain barrier model, we have compared the barrier properties...
Article
Carbamazepine and selegiline, although neuroprotective themselves, are presumed to have toxic metabolites. The aim of this study was to investigate the possible metabolism-induced toxicity of selegiline and carbamazepine with a novel in vitro method: The drugs were incubated with target cells (neuroblastoma SH-SY5Y) with or without a pre- incubatio...
Article
Machine vision is an application of computer vision. It both collects visual information and interprets the images. Although the machine obviously does not 'see' in the same sense that humans do, it is possible to acquire visual information and to create programmes to identify relevant image features in an effective and consistent manner. Machine v...
Chapter
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The Draize rabbit eye irritation test developed in the 1940's is even today the only eye toxicity test officially accepted in the OECD countries for regulatory purposes in the classification of slightly and moderately irritating chemicals. It is based on the subjective scoring of three tissues of the eye: the cornea, the conjunctiva and the iris. T...
Article
The cytotoxicity of amitriptyline (0-100microM), selegiline (0-4.5microM), carbamazepine (0-420microM) and paracetamol (0-10mM) was studied in metabolically competent mouse hepatocytes, metabolically incompetent human hepatoblastoma (HepG2) cells, and in neuroblastoma (SH-SY5Y) and astrocytoma (U-373 MG) cells, by using luminescence-based ATP measu...
Article
In this in vitro study, changes in the activity of the neural membrane integral protein, ATPase, were recorded after the exposure of isolated synaptosomes to different concentrations of aluminium and lead. Both total ATPase activity and Mg(2+)-ATPase activity were studied. A specific mouse strain, heterozygous for a glial cell line-derived neurotro...
Article
Pyrethroids are the most widely used insecticides for indoor pest control, so human exposure to them is common. The main target of pyrethroids is the nervous system, but their endocrine disrupting capabilities may also be of toxicological concern. In the present study, the proliferation of the breast cancer cell line, MCF7, was studied after a 7-da...
Article
Mercury and aluminum are considered to be neurotoxic metals, and they are often connected with the onset of neurodegenerative diseases. In this study, mercuric mercury, methylmercury and aluminum were studied in three different cell lines of neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis induced by the metals were...
Article
Evaluation of the effects of laser photocoagulation on cultured primary retinal pigment epithelial cells. Cells were treated by a diode laser (678 nm) with 800 and 1600 mW for 0.186 second. Cell toxicity was tested by the WST-1 assay, and the uptakes of glutamate and gamma-aminobutyric acid (GABA) were measured. Laser photocoagulation (1600 mW) cau...
Article
Glucose is the main energy source of brain cells. The transport of glucose across the cell membrane is the first step of its utilization. Any modification in glucose uptake capacity may cause deleterious effects on neural cell functions. In the present study, 3-O-methyl-D-glucose (3-OMG) uptake and its modulation by selected neurological drugs (ami...
Article
The effects of aluminium lactate (Al-lactate) on the rat cerebral synaptosome integral proteins adenosinetriphosphatase (ATPase) and acetylcholinesterase(AChE) were studied in vitro and in vivo. Coexposure with ethanol (EtOH) was studied in both situations. Isolation of synaptosomes was carried out using isoosmotic Percoll gradients. In in vitro ex...
Article
Glutamate is the major excitatory neurotransmitter in the retina and glutamate uptake is essential for normal glutamate signalling. Retinal diseases may induce neurochemical changes which affect retinal cells including retinal pigment epithelium (RPE). The aim of the study was to investigate the expression of glutamate transporter subtypes in RPE a...
Article
In this study, in vitro blood-brain barrier (BBB) models composed of two different cell types were compared. The aim of our study was to find an alternative human cell line that could be used in BBB models. Inorganic and organic mercury and aluminum were studied as model chemicals in the testing of the system. BBB models were composed of endothelia...
Article
Tamoxifen and toremifene are antiestrogenic drugs successfully used in the therapy of breast cancer. Rheumatoid arthritis and malaria have been treated with chloroquine for decades. Unfortunately, tamoxifen and chloroquine are reported to induce retinal changes as a side effect. We now studied the effects of tamoxifen, toremifene, and chloroquine o...
Article
Pyrethroids are important insecticides used largely because of their high activity as an insecticide and their low mammalian toxicity. Some studies have demonstrated that these products, especially compounds with an α-cyano group, show neurotoxic effects on the mammalian central nervous system (CNS). In this study, we investigate with different met...
Article
The transport of D-glucose into rainbow trout (Oncorhynchus mykiss) and river lamprey (Lampetra fluviatilis) hepatocytes, as well as into rainbow trout hepatoblastoma cell line RTH-149 was studied using tracer methods. The half-time for D-glucose equilibration was 15 s for rainbow trout. The half-times for the non-metabolizable D-glucose analog, 3-...
Article
The antioestrogens, tamoxifen and its more recent homologue toremifene, are used in the therapy of breast cancer. Tamoxifen has been reported to cause retinal changes as side effects. Both compounds inhibited glutamate uptake in retinal pigment epithelial cells, and the present study was conducted to clarify the mechanism of this inhibition. Retina...
Article
Full-text available
Alternatives to the Draize rabbit eye irritation test are currently being investigated. Because of morphological and biochemical differences between the rabbit and the human eye, continuous human cell lines have been proposed for use in ocular toxicology studies. Single cell-type monolayer cultures in culture medium have been used extensively in oc...
Article
Pyrethroids are used widely as insecticides both in agriculture and in households. A cellular target of pyrethroids is the sodium channel in the membrane. In the present study, the activity of the membrane bound integral protein ATPase was studied as a biomarker for the membrane effect of the pyrethroids permethrin and cypermethrin. Male Sprague-Da...
Article
The purpose of this paper is to review the current state of development of advanced in vitro blood-brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothel...
Article
Full-text available
This study was undertaken to investigate the use of the in vitro test WST-1, an assay of cell proliferation and viability, for a preliminary safety evaluation of topical ophthalmic preparations. The cytotoxicity of two surfactants, benzalkonium chloride (BAC) and polyoxyethylene-20-stearyl ether (Brij78, PSE) was independently investigated in four...
Article
Full-text available
5-Fluorouracil (5-FU) is commonly used in ophthalmology for suppressing fibroblast activity after glaucoma surgery. Adverse effects on corneal epithelial cells have been reported to relate to 5-FU therapy. The effects of 5-FU were evaluated in vitro on SV40-immortalized human corneal epithelial cell (HCE) cultures with two cytotoxicity tests: WST-1...
Article
The systemic drugs chloroquine and tamoxifen have caused retinal defects in human eye. The aim of our study was to investigate the effects of the amphiphilic drug tamoxifen, of its homologue toremifene, and of chloroquine on the glutamate uptake in retinal pigment epithelial (RPE) cells. Cultured human RPE cell line D407 and pig RPE cells were used...
Article
Full-text available
The cytotoxicity of benzalkonium chloride (BAC) and disodium edetate (EDTA) was evaluated in vitro in rabbit corneal epithelial primary cells and in the immortalized human corneal epithelial cell line SV40. Cell injury was assessed by lactate dehydrogenase (LDH) leakage and by reduction of the tetrazolium salt WST-1 to formazan by mitochondrial met...
Article
The cytotoxicity of the selected systemic and intravitreally dosed drugs tamoxifen, toremifene, chloroquine, 5-fluorouracil, gentamicin and ganciclovir was studied in retinal pigment epithelium (RPE) in vitro. The cytotoxicity was assayed in the human RPE cell line D407 and the pig RPE cell culture using the WST-1 test, which is an assay of cell pr...
Article
The neurotoxicity of lead is well known, but the exact mechanisms of its toxicity are not solved yet. Disturbances in glutamate homeostasis of neural tissue and interactions of lead with calcium metabolism have been considered as a potential mechanism. In the present study, we evaluate the acute effect of lead exposure by studying glutamate uptake,...
Article
The cytotoxicity of mercuric chloride and the effects of mercuric chloride on glutamate and calcium uptake and the factors regulating glutamate uptake were studied in retinal pigment epithelium (RPE) cell cultures. RPE cells isolated from pig eyes and human RPE cell line (D407) cells were cultured to confluency and further subcultured according to...
Article
The effects of tamoxifen, toremifene and chloroquine on the phagocytosis of rod outer segments by retinal pigment epithelium were evaluated in human retinal pigment epithelial cell line D407 and pig retinal pigment epithelial cell culture. Retinal pigment epithelial cells were exposed to different concentrations of tamoxifen (1–20 μM), toremifene (...
Article
A mini-review is presented of the current techniques for maintaining Müller cells in a culture. Within the retina, Müller cells are the predominant glial cells. These highly specialised cells extend over the entire neural retina. One of the most important of the various physiological functions of Müller cells is to regulate the balance of ions and...
Article
Pyrethrins are widely used insecticides in both agriculture and households. In many commercial formulations piperonyl butoxide (PBO) is used with pyrethrins. PBO is a well-known synergist of pyrethrins, used to intensify their effects. One of the cellular targets of pyrethrins is the sodium channel in the membrane. In the present study, the activit...
Article
This article reviews in vitro testing of retinal toxicity in retinal pigment epithelium (RPE) cell cultures. It is based on the literature on RPE cell cultures and on our recent studies on the retinal toxicity of selected amphiphilic drugs. The RPE plays a major role in maintaining the homeostasis and health of the retina. Various pharmacological a...
Article
Retinal pigment epithelial cells carry out phagocytosis and digestion of material shed from the photoreceptor outer segments. In this process, the integrity of lysosomal enzymes is of major importance. In the present study the effects of tamoxifen, toremifene and chloroquine on the activity of two lysosomal enzymes (cathepsin D and N-acetyl-β-D-glu...
Article
The anticancer drug tamoxifen is widely used in breast cancer therapy, Tamoxifen has been reported to cause ocular toxicity and impairment of vision in epidemiological studies To study the possible role of an excitotoxic mechanism in the ocular toxicity of tamoxifen, we investigated the effect of tamoxifen on retinal pigment epithelium (RPE) glutam...
Article
Organic solvents are widely used both in industry and in households. Misuse of organic solvents is common, and intoxications and sniffing episodes are not rare (Ikeda, 1992). Solvents belong to various chemical categories, including aliphatic, halogenated aliphatic, alicyclic and aromatic hydrocarbons, alcohols, ethers, ketones and other minor chem...
Article
Aliphatic, alicyclic and aromatic hydrocarbons interact with biological membranes. Until now little has been known about their mode of interaction with the membrane bilayer and membrane integral proteins with toxic effects to cells. The lipid theory hypothesis explains the toxic effects by the organic solvent-induced disorder in the lipid bilayer,...
Article
Purpose. Retinal pigment epithelium (RPE) accumulates some drugs within lysosomes. Retinopathy of tamoxifen and chloroquine has been reported. We studied in vitro the effects of chioroquine and the antiestrogenic drugs tamoxifen and toremifene on the activity of two lysosomal enzymes (cathepsin D and N-acetyl-β-D-glucosaminidase) in the RPE to asse...
Article
— There are several hundred industrial chemicals with neurotoxic potential. The neurotoxic risks of most of these chemicals are unknown. Additional methods are needed to assess the risks more effectively and to elucidate the mechanisms of neurotoxicity more accurately than is possible with the conventional methods. This paper deals with general tas...
Article
The effects of mercuric chloride, methylmercury chloride and aluminium chloride on glial fibrillary acidic protein (GFAP) expression in primary cerebellar astrocyte cultures were studied. GFAP has been found to be a quantitative marker of neuronal injuries on the central nervous system in vivo. The GFAP content of the astrocytes was examined by san...
Article
1. The present study deals with astrocyte cultures as a model for studying the membrane-mediated central nervous system-depressing effect of organic solvents. 2. The primary astrocyte cultures were prepared from neonatal rat cerebella. The cells were cultured in modified essential medium. The astrocyte membranes isolated from the cultures were expo...
Article
The retinal pigment epithelium (RPE) removes the outer segments of photoreceptor cells by phagocytosis. We studied the effects of tamoxifen and chloroquine on the activity of the lysosomal enzymes N-acetyl-beta-glucosaminidase and cathepsin D in RPE in vitro to evaluate the possible eye toxicity caused by these drugs. The results show decreases in...
Article
Astrocytes serve to maintain the proper homeostatic environment for neurons. In these regulations, the astrocyte membrane ATPase plays an important role. In the present study, the astrocyte were cultured in the modified Minimum Essential Medium (MEM), and the isolated cell membranes were exposed to solvents at different concentrations (3, 6 and 9 m...
Article
The most common acute neurotoxic effect of organic solvents is their central nervous system (CNS) depressant effect. The molecular mechanism underlying this effect is not known. The purpose of our studies has been to evaluate the adverse effects of organic solvents on the CNS in vitro. Synaptosomal membranes, whole brain reaggregate and astrocyte c...
Article
The aim of the study was to evaluate astrocytes in vitro as a model for studies of solvent neurotoxicity. Primary astrocyte cultures were established from newborn rat cerebella. The cells were cultured in the modified Minimum Essential Medium (MEM), and the neural membranes isolated from cultures were exposed to solvents in incubation mixtures cont...
Article
The effects of benzene, ethylbenzene, styrene and toluene on rat synaptosomal membrane fluidity and the activities of integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosomal membranes were isolated in Percoll gradients. After adding 2, 4, 6 and 8 mM concentrations of organic solvents to the incubation mixture...
Article
The effects of toluene and n-hexane on rat synaptosomal membrane fluidity and the integral enzymes acetylcholinesterase (AChE) and ATPase were studied in vitro. The synaptosome membranes were isolated in Percoll and sucrose gradients. After adding toluene and n-hexane to the incubation mixture (37 degrees) in 2,4,6 and 8 mM concentrations, the flui...
Article
The structural organization of membrane proteins and their interaction with lipids renders them sensitive to perturbations of organic solvents. Some membrane proteins are inhibited up to 50 per cent at the anaesthetic concentration of many inhalation anaesthetics, aliphatic and aromatic hydrocarbons, alcohols, ketones, esters and alkanes (Franks an...
Article
Organic solvents may exert their anaesthetic effect on central nervous tissue by affecting the cell membrane integral enzymes, which regulate the ion transport through the membrane (Korpela and Tähti 1986). In the present study, the effect of n-hexane and its metabolites 2,5-hexanedione, 2-hexanol and 2-hexanone on membrane acetylcholinesterase (AC...
Article
The aim of the present study was to find a method for in vitro studies of the neurotoxic mechanism of industrial solvents. The effects of carbon disulphide and n-hexane and its metabolites were studied. Cell membrane changes were studied by measuring changes in the activity of the integral cell membrane enzymes acetylcholinesterase (AChE) and adeno...
Article
The effects of toluene, trichloroethylene and ethanol on membrane acetylcholinesterase (AChE) activity in human and rat intact erythrocytes and erythrocyte ghosts were studied in vitro over a range of concentrations (300-3000 ppm) and at three different incubation temperatures (37, 15 and 5 degrees C). Toluene and trichloroethylene decreased the AC...
Article
The mechanism of the anaesthetic effect of toluene on the central nervous system (CNS) was studied by using rat erythrocyte and synaptosome membranes as nerve cell models both in vitro and in vivo. The activities of the membrane-bound integral enzymes acetylcholinesterase (AChE), total adenosine triphosphatase (total ATPase) and magnesium-activated...
Article
Trichloroethylene (TCE) is a widely used organic solvent, the most important toxic effect of which is a narcotic central nervous (CNS) effect. In the present study we have used rat erythrocyte membranes as a nerve cell model for studying the changes in membrane integrity caused by TCE treatment. The parameters determined were osmotic resistance and...
Article
The effects of some aromatic hydrocarbons, aliphatic chlorinated hydrocarbons, and alcohols on adenosine triphosphatase (ATPase) activity in human erythrocyte ghost membrane were studied in vitro. Both aromatic and chlorinated aliphatic hydrocarbons inhibited this activity dose-dependently, the inhibition of total ATPase activity being clearer than...
Article
Human erythrocytes were exposed to different concentrations of aromatic hydrocarbons, chlorinated aliphatic hydrocarbons, and alcohols in vitro to study the effects of these agents on the activity of acetylcholinesterase (AchE), a membrane integral protein. Aromatic hydrocarbons were in general more potent AchE inhibitors than chlorinated aliphatic...
Article
Adult male rats were exposed to toluene in short-term exposure by inhalation for 48 h (2000 ppm, continuously), and in long-term inhalation for 3 months (1000 ppm, 8 h daily). The formaldehyde-induced fluorescence (FIF) technique for histochemical demonstration of catecholamines (CA) was used to detect changes in the catecholamine stores. The conce...
Article
To study the effects of aromatic hydrocarbons, chlorinated aliphatic hydrocarbons, and alcohols on erythrocyte membrane, changes in the membrane-bound acetylcholinesterase (AchE) activity were tested after solvent treatment by the Ellman method. When the maximal effects of these solvents were tested at +37 degrees C, they diminished the AchE activi...
Article
In the present study, the effects of several organic solvents on human erythrocyte membrane acetylcholine esterase activity were tested in vitro with the Ellman method. All the organic solvents studied decreased the enzyme activity. The effects of aromatic hydrocarbons were greater than the effects of chlorinated aliphatic hydrocarbons. The effect...
Article
The antihemolytic effects of toluene were studied with inhalation exposures in vivo. At a concentration of 2000 ppm the effect seemed to begin 0.5 h after the onset of exposure, and it ended completely 0.5 h after the end of the exposure. There was no significant change in the mean corpuscular volume (MCV), although it increased at first during and...
Article
A coupola-shaped Plexiglass inhalation chamber (volume 190 I) with continuous infusion of toxicant and air flow was constructed for small laboratory animals. The method guarantees an even distribution of vapourized toxicant to 16 animals at the same time, and is convenient both in short-term and long-term experiments. As a volatile toxicant, toluen...
Article
The effect of toluene on rat erythrocyte hemolytic resistance was studied both in vitro and in vivo. In vitro, toluene at concentrations up to 1000 ppm showed a marked antihemolytic effect, the maximum being at 300 ppm. Above 1000 ppm, an increase in the hypotonic hemolysis was seen. The antihemolytic effect of toluene was temperature-dependent. El...
Article
Chronic occupational exposure to toluene was studied in a factory preparing tarpaulins. Seventy-eight workers were studied; 46 were exposed to various concentrations of toluene in air (20--200 ppm), 32 were unexposed workers in the same factory. In many cases the exposure had lasted for 10--20 years. The urinary hippuric acid excretion at the end o...
Article
Respiratory and circulatory differences between periodic spontaneous arousals and induced arousals in hibernating hedgehogs were studied in a constant ambient temperature of + 4.2 +/- 0.5 oC. The increase in O2 consumption, blood pressure and heart rate was faster during induced arousals than during periodic spontaneous arousals. Based on our prese...
Article
The uptake, distribution, and elimination of 3H-toluene in various tissues of rats were studied after inhalation or after gastric intubation. The maximum radioactivity was measured 2–3 h after gastric intubation in tissues, except in white adipose tissue, where the peak radioactivity was reached at 5 h. After inhalation exposure, the uptake to vari...