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    Cyclic-AMP reception and cell recognition in dictyostelium discoideum
    (1975) Gerisch, Günther; Malchow, Dieter; Huesgen, Adolfine; Nanjundiah, Vidyanand; Roos, Werner; Wick, Ursula; Hülser, Dieter F.
    Single cells of the slime mold, Dictyostelium discoideum, aggregate into a multicellular organism in response to cyclic AMP, which they detect by binding to cellsurface receptors. During the aggregation phase, two different responses to cyclic-AMP are observed. First, the cells orientate by chemotaxis towards the source of a concentration gradient which initially is a group of cells forming an aggregation center. Second, the cells relay pulses which are periodically generated by the centers.
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    Nervous-system-specific carcinogenesis by ethylnitrosourea in the rat: molecular and cellular aspects
    (1977) Rajewsky, Manfred F.; Augenlicht, Leonard H.; Biessmann, Harald; Goth, Regine; Hülser, Dieter F.; Laerum, Ole D.; Lomakina, L. Ya.
    A lead in the search for cellular determinants favoring neoplastic transformation may be provided by the pronounced tissue specificity of the oncogenic effect of certain carcinogens which do not require enzymatic metabolic activation, i.e., in cases where this specificity cannot be due to tissue differences in the activity of enzymes involved in the formation of the ultimate reactants. A carcinogen that fulfills this condition is the ethylating agent N-ethyl-N-nitrosourea (EtNU). Alkylation of nucleic acid constituents by N-nitroso compounds in relation to mutagenesis and carcinogenesis has received considerable attention recently.
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    Molecular and cellular mechanisms in nervous system-specific carcinogenesis by N-ethyl-N-nitrosourea
    (1976) Rajewsky, Manfred F.; Goth, Regine; Laerum, Ole D.; Biessmann, Harald; Hülser, Dieter F.
    A single pulse of N-ethyl-N-nitrosourea (ENU), applied to BDIX rats during the perinatal age, specifically results in a high incidence of neuroectodermal neoplasms in the central and peripheral nervous system (NS). The pronounced sensitivity of the developing NS suggests a dependence of the carcinogenic effect on the proliferative and/or differentiative state of the target cells at the time of the ENU pulse. The specificity of ENU for the NS cannot be due to tissue variations in the degree of carcinogen-cell interactions, since the reactive, electrophilic ethyl cation is produced by rapid, nonenzymatic decomposition of ENU indiscriminately in all tissues. Correspondingly, the initial molar fractions of ethylated purine bases are similar in the DNA of "high-risk" (perinatal brain) and "low-risk" tissues (e.g., liver; adult brain). However, while the respective half lives in DNA of N7-ethylguanine and N3-ethyladenine show only minor differences for both types of tissues, the mutagenic ethylation product 06-ethylguanine is removed from brain DNA very much more slowly than from the DNA of other tissues. Together with their high rate of DNA replication during the perinatal age, the incapacity of rat brain cells for enzymatic elimination of 06-alkylguanine from their DNA could account for an increased probability of neoplastic conversion, and hence for the NS specificity of ENU in the rat.
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    Survival and chromosome injury of spheroid cells after irradiation
    (1979) Dertinger, Hermann; Hülser, Dieter F.; Hinz, Gudrun
    Multicell spheroids (SPH) offer unique advantages for studying modifications of single cell radiosensitivity due to the extensive intercellular communication in a three-dimensionally organized tissue. We have been able to relate the increased radio-resistance of spheroid cells as compared to monolayer (ML) cells ("Contact Resistance") to the degree of ionic coupling between the cells as measured by a micro-electrode technique.
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    Electronmicroscopical and electrophysiological investigations on polyethylene glycol induced cell fusion
    (1978) Krähling, Hermann; Schinkewitz, Ursula; Barker, Angela; Hülser, Dieter F.
    Cells of monolayer cultures are fused by high concentrations of polyethylene glycol (PEG) with a molecular weight of approximately 1500. This process is independent of extracellular ca++ions. PEG changes transiently the surface membrane and leads to fusion only after replacing it by normal medium. Before the final fusion of two cells, the onset of ionic coupling via longer lasting pseudopodial contact can be measured. Only cells that are synchronous in the secretory and pseudopodial response to PEG may fuse with each other.
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    Membrane properties of cultured cells
    (1976) Hülser, Dieter F.
    Intercellular communication is a prerequisite for intact organisms especially during development and differentiation, and occurs as regulation over long distances (hormones), as short distance interactions (synapses) or as direct cell to cell contact. The direct cell contact is enabled by specialized membrane areas, the so called gap junctions, which allow not only the passage of ions (ionic coupling) but also of larger molecules (metabolic cooperation). The identity of these three coupling phenomena was demonstrated with cell cultures, where hormonal or neuronal regulatory processes can be excluded.
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    Electrophysiological properties of ethylnitrosourea-induced, neoplastic neurogenic rat cell lines cultured in vitro and in vivo
    (1976) Laerum, Ole D.; Hülser, Dieter F.; Rajewsky, Manfred F.
    A comparative analysis was performed on the electrophysiological properties of 11 neoplastic neurogenic cell culture lines and five other cell lines of different origin (HV1C, rat bile duct carcinoma; BICR/M1 RK , rat mammary tumor; HeLa, human cervix carcinoma; 3T3, mouse embryo; REe, rat embryo). Neurogenic lines were derived either from N-ethyl-N-nitrosourea-induced neoplasms of the nervous system or from cultured fetal rat brain cells that had undergone neoplastic transformation in vitro after exposure to Nethyl-N-nitrosourea in vivo. Electrical membrane excitability was lacking in all neurogenic cells analyzed. Their membrane potential and input resistance values were similar to those of the nonneurogenic lines. Intercellular ionic coupling was consistently observed between cells of a fibroblastoid shape or cells bearing multiple cytoplasmic processes (i.e., all neurogenic lines HV1C, BICR/M1RK , and 3T3). Epithelioid cells (i.e., HeLa, REe, an NV1C subpopulation, and a GV1C1 variant) showed no such intercellular communication. In vivo monolayer cultures on glass coverslips were obtained by a modified i.p. diffusion chamber technique. Under these conditions, the cells (with the exception of a glioma-derived cell line) retained the morphological appearance and electrophysiological properties observed in vitro.