Dietmar Schiffmann's research while affiliated with University of Rostock and other places

Publications (111)

Article
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Epidemiological and experimental studies have suggested the enhancement of asbestos-induced disease processes by simultaneous exposure to kerosene, its soot, and cigarette smoke in asbestos-exposed animals as well as in humans. To determine the influence of these factors on the genotoxic potential of asbestos, a micronucleus test was performed in S...
Article
Glucocorticosteroids (GCS) are widely used for the treatment of neurological diseases, e.g. multiple sclerosis. High levels of GCS are toxic to the central nervous system and can produce adverse effects. The effect of methylprednisolone (MP) on mammalian neuronal networks was studied in vitro. We demonstrate a dose-dependent excitatory effect of MP...
Article
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Nanomaterials are extensively used in industry and daily life, but little is known about possible health effects. An intensified research regarding toxicity of nanomaterials is urgently needed. Several studies have demonstrated that nanoparticles (NPs; diameter < 100 nm) can be transported to the central nervous system; however, interference of NPs...
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Nanotechnology presents countless opportunities to develop new and improved consumer products for the benefit of society. However, as the industrial production and use of nanotechnology products continue to expand at a fast scale, potential human health concerns and ecological safeguards for the environment need to be addressed. Health risk assessm...
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Four tumour suppressor genes (Chk1, Chk2, Apaf1 and Rb1) in nine human malignant melanoma cell lines were screened for a loss of gene expression, point mutations and small deletions/insertions by cDNA-based DGGE/SCCP analysis. In two cell lines alterations of the investigated genes could be demonstrated. This result confirms our assumption of the p...
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The innovative alternative method of multielectrode neurochip recording, which offers improvements compared to standard animal experimentation, has been further optimised by advanced multi-parametric data analysis and used to study toxicity patterns of known toxicants. Neuronal networks on 64-electrode neurochips develop long-term stable spontaneou...
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Developments in the field of molecular epidemiology and toxicology have given valuable tools for early detection of impending disease or toxic condition. Morbidity due to respiratory distress, which may be due to environmental and occupational exposure, has drawn attention of researchers worldwide. Among the occupational exposure to respiratory dis...
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Eighteen congenital melanocytic naevi (CMN) from 17 patients and 18 dysplastic melanocytic naevi (DMN) from 18 patients were screened for mutations in the BRAF oncogene (present study) and the N-ras oncogene (in the course of two foregoing studies) by single-strand conformational polymorphism (SSCP)/sequencing analysis. BRAF mutations were demonstr...
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Seven tumour suppressor genes (Chk1, Chk2, Apaf1, Rb1, p53, p16(INK4a) and p14(ARF)) and two oncogenes (N-ras and BRAF) were screened in nine human malignant melanoma (HMM) cell lines for point mutations or small deletions/insertions by DGGE, TGGE and SCCP analysis. For the first time in human mesothelioma, Chk1 gene mutations were detected in two...
Article
Asbestos fibers are well known environmental carcinogen, however, the underlying mechanisms of their action have still not clearly been identified. Asbestos is capable of depleting glutathione and generating reactive oxygen species (ROS), which are important mediators of damage in biological system. Asbestos-induced mutagenecity, may be mediated by...
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The genotoxicity of asbestos fibers is generally mediated by reactive oxygen species (ROS) and by insufficient antioxidant protection. To further elucidate which radicals are involved in asbestos-mediated genotoxicity and to which extent, we have carried out experiments with the metal chelators deferoxamine (DEF) and phytic acid (PA), and with the...
Article
It is well known that asbestos fibers induced genotoxicity is mediated by reactive oxygen species (ROS) and insufficient endogenous antioxidant protection. Asbestos exposure can result in ROS generation in two different ways: (a) by catalyzation of Fe(2+), which is present in asbestos fibers, and (b) via oxidative bursts during phagocytosis of the...
Article
Fourteen primary human malignant mesothelioma (HMM) samples obtained from 14 patients were screened for point mutations and microdeletions/microinsertions in exons 1-16 of the chromosome 22q-located tumour suppressor gene neurofibromin 2 (nf2) by single strand conformation polymorphism (SSCP) analysis. In one tumour (7%) a 10 basepair microdeletion...
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In order to detect possible dysplastic melanocytic naevi (DMN) associated melanoma risk factors and lesion specific differences in the mutation spectrum of dysplastic and congenital melanocytic naevi (CMN), we screened 19 specimens of human sporadic DMN derived from 19 patients for the presence of mutations in five genes, which we had investigated...
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Several experimental and epidermological studies have indicated augmentation of asbestos induced diseases by cigarette smoke by the mechanisms, which are still unknown. To determine whether smoking affects genetic system of the cells and further modifies asbestos induced genotoxicity, whole blood from non-smokers and smokers was exposed to asbestos...
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Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes...
Article
Eighteen primary human malignant mesotheliomas obtained from 18 patients were screened for point mutations and microdeletions/insertions in all exons of the tumour suppressor gene PTEN/MMAC1 by SSCP analysis. No mutation could be found. Our preliminary data indicate that disarrangements of PTEN/MMAC1 are at least not frequently involved in mesothel...
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Nineteen specimens from primary human malignant mesotheliomas obtained from 19 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 by combined RFLP-PCR/SSCP analysis. In addition, all tumours were screened for deletions and point mutations in the tumour suppressor genes p53, p16INK4a (CDKN2A) and p14ARF (exon-1beta...
Article
We used spontaneously active monolayer networks in vitro, cultured on thin film microelectrode arrays as experimental platforms for the determination of trimethyltin chloride (TMT) toxicity. Two different tissues of the mouse CNS (spinal cord and auditory cortex) exhibited characteristic and dose-dependent changes of their electrophysiological acti...
Article
Epidemiological and experimental studies have suggested an enhancement of asbestos-induced bronchogenic carcinoma by cigarette smoke. Further, our recent experimental and epidemiological studies have indicated that besides smoking, several other compounds including kerosene soot may accelerate disease processes in asbestos-exposed animals as well a...
Article
Glutathione (GSH) is a ubiquitous intracellular thiol present in all tissues, including lung. Besides maintaining cellular integrity by creating a reduced environment, GSH has multiple functions, including detoxification of xenobiotics, synthesis of proteins, nucleic acids, and leukotrienes. Present in high concentrations in bronchoalveolar lavage...
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In order to clarify the relationship between delayed reproductive death and radiation-induced genomic instability, the colony-forming efficiency of surviving, irradiated human squamous carcinoma cells and centromere positive as well as centromere negative micronuclei in surviving progeny were examined. Colony-forming ability and micronucleus (MN) f...
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Eighteen human congenital melanocytic naevi (CMN) from 17 patients were screened for activating point mutations in the oncogenes N-ras and CDK4 and for sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in the tumour suppressor genes p53 and p16INK4a (CDKN2...
Article
The mycotoxin ochratoxin A (OTA) is a naturally occuring contaminant of food. The genotoxic status of OTA is still controversial because contradictory results were obtained in various microbial and mammalian gene mutation assays. In this study, OTA was investigated to examine its potency to induce micronuclei (MN) in SHE cells. The SHE-micronucleus...
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The use of mammalian cell systems for recombinant protein production has become the dominant method to produce high-value proteins for therapeutic purposes. Recombinant cell lines are often generated by transfection with specific DNA; therefore a selectable system is desirable to discriminate cells that have integrated the foreign DNA. Chinese hams...
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In previous investigations it was shown that the synthetic estrogen diethylstilbestrol (DES) induces a rise of the intracellular calcium level ([Ca2+]i) in C6 rat glioma cells [P. Tas, H. Stopper, K. Koschel, D. Schiffmann, Influence of the carcinogenic oestrogen diethylstilboestrol on the intracellular calcium level in C6 rat glioma cells. Toxic....
Article
Eighteen human congenital melanocytic naevi (CMN) from 17 patients were screened for activating point mutations in the oncogenesN-ras andCDK4 and for sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in the tumour suppressor genesp53 andp16INK4a(CDKN2A) by...
Article
Full-text available
Asbestos and other mineral fibers have long been known as carcinogenic agents. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We have investigated mitotic disturbances caused by amosite, crocidolite, and chrysotile in Syrian hamster embryo (SHE) fibroblasts. We also analyzed micronucleus formation as a result...
Article
The centric/pericentric region of chromosome 1 (cen-q 2) of human melanoma cells of different stages of carcinogenicity (superficial spreading melanoma (SSM), lentigo malignant melanoma (LMM)) and premalignant precursor lesions (congenital nevus (CN)) were investigated by fluorescence in situ hybridization (FISH) with tandem DNA probes. The pericen...
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This article describes the induction of micronuclei, hyperdiploidy and chromosome breakage in human amniotic cells in vitro by amosite, chrysotile and crocidolite asbestos, and ceramic fibers. The response of human (amniotic fluid cells) and rodent (Syrian hamster embryo fibroblasts, SHE) cells to fiber treatment was compared using the micronucleus...
Article
Asbestos and other mineral fibers have long been known as carcinogenic agents. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We have investigated mitotic disturbances caused by amosite, crocidolite and chrysotile in Syrian hamster embryo (SHE) fibroblasts. We have analyzed micronucleus formation as a result o...
Article
While the accumulation of genetic changes in a somatic cell is considered essential for the genesis of a cancer, it has become clear that not all carcinogens are genotoxic, suggesting that some carcinogens indirectly participate in the generation of genetic changes during carcinogenesis. A European project funded by the European Community was thus...
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In this study we analysed snap-frozen surgical resections of 16 superficial spreading melanomas, 13 nodular malignant melanomas, 2 lentigo maligna melanomas, 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi from 38 patients for point mutations in the human p53 gene at exons 5-8 by polymerase chain reaction/single-strand conformation polymor...
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Leukemia of the soft shell clam, Mya arenaria, is characterized by circulating tumor cells detected initially in the hemolymph and, as the disease progresses, in solid tissue. Because they are estuarine filter-feeders, clams are exposed to a wide variety of environmental pollutants. Genotoxic pollutants may react directly in vivo with DNA. Genotoxi...
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Although the synthetic estrogen diethylstilbestrol (DES) is an established carcinogen, little is known about its mechanisms of tumor induction. It is considered a nonmutagenic carcinogen inducing aneuploidy via chromosomal nondisjunction. However, it is still unclear if DES interacts with DNA directly. The degree of cytosine methylation of specific...
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An altered DNA methylation pattern is one of the possible consequences of mammalian neoplasia and also occurs in cultured cells after treatment with certain toxic or carcinogenic substances. Another consequence which can often be seen in the same cells is genomic instability. Analysis of micronucleus frequencies and chromosome numbers in primary an...
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The aneuploidy-inducing carcinogenic oestrogen diethylstilboestrol (DES) causes an elevation of the cytoplasmic Ca(2+) concentration of C6 rat glioma cells. It is known that the intracellular calcium concentration is a critical factor in mitosis. DES induces mitotic disturbances resulting in aneuploidy; the mechanisms of these events are still larg...
Article
Full-text available
Asbestos and other mineral fibers have long been known to induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain unclear. We investigated the occurrence of mitotic disturbances induced by asbestos (amosite, crocidolite, chrysotile) in an in vitro approach using Syrian hamster embryo (SHE) f...
Article
We have analyzed the Ha-ras, Ki-ras and N-ras gene for point mutations at codons 12, 13 and 61 via restriction fragment length polymorphism/polymerase chain reaction analysis and subsequent direct sequencing in non-cultured fresh-frozen tissues of 16 superficial spreading melanomas (SSM), 13 nodular malignant melanomas (NMM), 2 lentigo malignant me...
Article
Full-text available
It is known that asbestos and other mineral fibers induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain to be elucidated. Previous studies, including our own, have shown that asbestos causes specific mitotic disturbances, micronucleus formation and typical changes in chromatin structure r...
Article
This study was designed to investigate a previously unidentified potential mechanism for mutation induction as well as to clarify a biological consequence of micronucleus formation. We compared the induction of micronuclei with mutation induction as measured by trifluorothymidine (TFT) resistance in mouse L5178Y cells using four aneugens: colcemid,...
Article
Two analogues of the carcinogenic oestrogen diethylstilboestrol (DES), indenoestrol A (IA) and indenoestrol B (IB), have been studied with respect to their genotoxic and cell transforming properties in mammalian cells. The conformation and oestrogenicity of IA and IB are very similar, but they differ with respect to their ease of peroxidation and t...
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In chronic helminthic infections such as cysticercosis, where the parasites live for years, profound modulation of the host immune response has been reported. To evaluate the genotixicity of a drug used to treat cysticercosis, we observed the occurence of genetic damage in cultured lymphocytes from cysticercotic swine and patients who had not been...
Article
Praziquantel, a drug used for the treatment of neurocysticercosis, was tested for its ability to induce morphological transformation of Syrian hamster embryo fibroblasts. Results indicate that praziquantel transforms these cells without affecting their viability. Further experiments were carried out to investigate its possible mechanism of action i...
Article
In addition to its tumor-promoting activity in hormone-receptive tissue, the carcinogenic estrogen diethylstilbestrol (DES) has been found to induce cell transformation, aneuploidy and micronucleus formation in mammalian cells. The majority of these micronuclei contained whole chromosomes and were formed during mitosis. Here a possible relationship...
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Full-text available
The insecticide buprofezin was examined for its genotoxicity in cultured Syrian hamster embryo cells in order to better understand the mechanisms underlying the genotoxicity of the compound in mammalian cells. Exposure to buprofezin concentrations of 12.5-100 microM did not significantly affect the colony-forming ability of the cells, but did resul...
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The benzodiazepines are a class of drugs that are widely used in the treatment of various psychiatric disorders. One member of this class, oxazepam, is also a common metabolite of several other benzodiazepines. Since the evidence for the genetic toxicity and carcinogenic properties of these compounds is inconsistent, we investigated the oxazepam-in...
Article
Seventy-five chemicals, carcinogens and noncarcinogens, were tested in the SHE (Syrian hamster embryo) micronucleus test in vitro. Substances inducing a reproducible and dose dependent increase in micronucleus frequency were regarded as positive. The acquired data were analyzed for correlations with results obtained from the in vivo mouse bone marr...
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5-Azacytidine was originally developed to treat human myelogenous leukemia. However, interest in this compound has expanded because of reports of its ability to affect cell differentiation and to alter eukaryotic gene expression. In an ongoing attempt to understand the biochemical effects of this compound, we examined the effects of 5-azacytidine o...
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Some chromosomes in transformed rat cells and somatic cell hybrids fail to display the presence of kinetochore proteins as detected by antikinetochore antibodies. Such chromosomes (K- chromosomes) may constitute a novel mechanism for the genesis of aneuploidy. We have analyzed primary, immortalized and malignant mammalian cells for the presence of...
Article
1,2-Dioxetanes, very reactive and high energy molecules, are involved as labile intermediates in dioxygenase-activated aerobic metabolism and in physiological processes. Various toxicological tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonuclease-sensitive sites, most of them are FPG prot...
Article
Diethylstilbestrol (DES) is a synthetic estrogen with carcinogenic properties. DES is known to alter cytoskeletal components, including the organization of actin stress fibres in C6 rat glioma cells. In a test of the hypothesis that DES disrupts actin filaments of growth cones in neuron-like cells, DES-induced changes in filopodial lengths were qua...
Article
It is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic and/or gene mutation-inducing potential are still controversi...
Article
Sorbic acid, sodium sorbate and potassium sorbate were tested for their genotoxic potential in the Syrian hamster embryo (SHE) fibroblast micronucleus assay and the SHE cell transformation test in vitro. Sorbic acid and potassium sorbate showed no activity in either test system. When freshly prepared sodium sorbate solutions were used, no genotoxic...
Article
Organophosphates have previously been tested for the induction of delayed neuropathy in adult hens. An alternative in vitro test, which avoids the severe suffering caused by the test in hens, has been developed using permanent cell lines from a rat-brain glioma (C-6) or from a mouse-brain neuroblastoma (N-18). Addition of dibutyryl cAMP to these ce...
Article
The synthetic oestrogen diethylstilboestrol (DES) causes a dose-dependent elevation of the cytoplasmic Ca(2+) concentration in C6 rat glioma cells. This Ca(2+) rise is caused neither by Ca(2+) influx nor by release from the Ca(2+) stores of the endoplasmic reticulum. Therefore it seems likely that DES mobilizes Ca(2+) from a mitochondrial source. T...
Article
Some chromosomes in the rat do not have detectable levels of kinetochore proteins as determined by antikinetochore antibody, which may constitute a mechanism for the genesis of aneuploidy. An analysis of three mouse cell lines for the presence of kinetochore proteins showed that some chromosomes lacked these proteins, i.e. are akinetochoric by this...
Article
(trans,trans)-Muconaldehyde, a putative metabolite of benzene, should be expected to have mutagenic properties by virtue of its twin alpha,beta-unsaturated carbonylic function. It displayed definitely mutagenic properties in S. typhimurium TA100 without metabolic activation and with a 5-fold concentration of tester organisms in the preincubation as...
Article
The mechanisms of estrogen-induced cancer are still a matter of debate. Previous studies with stilbene estrogens and steroidal estrogens have shown that the in vitro transformation of primary Syrian hamster embryo (SHE) fibroblasts is a good experimental system for discriminating hormonal from nonhormonal events. We have now extended these studies...
Article
The in vitro micronucleus test with Syrian hamster embryo (SHE) cells assays the induction of micronuclei by chemical agents. Both chromosome fragments and lagging chromosomes can give rise to micronuclei. Nevertheless, only limited information is available on the ultrastructure of micronuclei and the mechanisms of their formation. Diethylstilbestr...
Article
http://deepblue.lib.umich.edu/bitstream/handle/2027.42/47534/432_2005_Article_BF01625409.pdf