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D F Hülser

Publications and source records attributed to D F Hülser.

At least 37 records · Page 2Linked to original sources
PubMed1990

Tumor cell invasion and gap junctional communication. I. Normal and malignant cells confronted in monolayer cultures.

Mammary tumor cells of the rat (BICR/M1Rk) and mouse (EMT6/Ro) as well as rat glioma cells (C6) are electrically coupled and show intercellular dye spreading. Monolayer cultures of synchronously beating chicken heart cells were also electrically coupled, dye spreading, however, was significantly restricted to only one or two adjacent cells. In all coupled cells, gap junctions were found in both freeze-fracture replicas and ultrathin sections. Heterologous gap junctional coupling between these tumor cells and heart cells was regularly established. The human cervix carcinoma line HeLa and the mouse L sarcoma line were electrically not coupled and did not reveal gap junctions, consequently they showed no coupling to heart cells.

Action Potentials↗
PubMed1990

Tumor cell invasion and gap junctional communication. II. Normal and malignant cells confronted in multicell spheroids.

The invasive behavior of five tumor cell lines was investigated with an in vitro invasion assay developed by Mareel et al. Spheroids of all 5 cell lines readily attached to precultured heart fragments (PHF), resulting in confronting pairs. Tumor cells (BICR/M1Rk, C6, and EMT6/Ro) which communicated with the host tissue via gap junctions, rapidly invaded the PHF within 3 days. Population doubling time or migratory activities had no influence on the invasion process. The noncoupled HeLa and L cells formed a cellular capsule around the PHF and showed no invasive activities. HeLa cells, however, started to destroy the PHF after 4 days. We suggest a mechanism different from that of coupled tumor cells. Epithelioid HeLa cells are linked by numerous tight junctions and may, therefore, cut off the nutrition supply for the inner-laying PHF, resulting in a disintegration of the heart tissue.

Animals↗
PubMed1989

Hydrogen ion-mediated enhancement of cytotoxicity of bis-chloroethylating drugs in rat mammary carcinoma cells in vitro.

Aerobic glycolysis, a metabolic characteristic of malignant cells, can be exploited to increase the concentration of lactic acid selectivity in tumor tissues in vivo by systemic administration of glucose (E. Jähde and M. F. Rajewsky, Cancer Res., 42: 1505-1512, 1982). To investigate whether a more acidic microenvironment can enhance the effectiveness of cytocidal drugs, we have analyzed the colony-forming capacity of M1R rat mammary carcinoma cells exposed to bis-chloroethylating agents in culture as a function of extracellular pH (pHe). At pHe 6.2 the cytotoxicity of 4-hydroperoxycyclophosphamide, as measured by inhibition of colony formation, was potentiated by a factor of approximately 200 as compared to pHe 7.4. Similar results were obtained with mafosfamide, nitrogen mustard, nornitrogen mustard, melphalan, and chlorambucil; not, however, with ifosfamide. As indicated by experiments using the ionophor nigericin for rapid equilibration of pHe and intracellular pH (pHi; measured with pH-sensitive microelectrodes), modulation of drug action by varying pHe primarily resulted from the concomitant decrease in pHi. The acidic microenvironment enhanced cytotoxicity most effectively during the phase of cellular drug uptake and monofunctional alkylation of DNA. DNA cross-link formation appeared to be less affected by pH, and lowering of pHe during the phase of cross-link removal was only marginally effective.

Alkylating Agents↗
PubMed1989

Effect of shock waves on suspended and immobilized L1210 cells.

L1210 mouse leukemia cells have been exposed to different doses of shock waves generated by underwater spark discharge at 18 kV in an experimental lithotripter (XL1, Dornier). Histological and flow cytometric investigations revealed severe damage and a LD50 of about 420 shock waves when the cells were treated as suspensions. Cells immobilized in gelatine, however, were unaffected, indicating that secondary effects are responsible for the cellular damage. Possible mechanisms such as cavitation, jets, and shear forces are discussed.

Animals↗
PubMed1988

Gap junction formation in rabbit uterine epithelium in response to embryo recognition.

Gap junction formation was studied in the uterine epithelium of nonpregnant, pregnant, and pseudopregnant rabbits in the periimplantation phase (6, 7, 8 days post coitum/post human gonadotropin injection) using freeze-fracture and immunocytochemistry as well as intracellular Lucifer yellow injection. At implantation (7 days post coitum) the uterine epithelial cells of the implantation chamber become junctionally coupled as evidenced by all three methods used. Gap junction protein (26K) becomes detectable immunocytochemically with a monoclonal antibody at 6 days post coitum in the epithelium surrounding the blastocyst, i.e., in the forming implantation chamber. The same sequence of events, starting with the presence of the gap junction protein before cell-to-cell coupling becomes evident, was observed in the blastocyst-free segments 1 day later. In contrast, uterine epithelium of nonpregnant and pseudopregnant animals in comparable phases shows an extremely low degree of coupling. The presence of the blastocyst is a necessary condition for the induction of gap junctions as demonstrated by unilateral pregnancy produced by tubal ligation. Thus, gap junction formation is one of the first maternal responses to a locally acting signal of the blastocyst.

Animals↗
PubMed1984

Comparative measurements of membrane potentials with microelectrodes and voltage-sensitive dyes.

The usefulness of a new voltage-sensitive fluorescent dye, the membrane permeant negatively charged oxonol dye diBA-C4-(3)-, was evaluated by measuring the membrane potentials of BICR/M1R-k and L cells with glass microelectrodes and simultaneously recording the fluorescence of the stained cells. The membrane potential of BICR/M1R-k cells was varied between -25 mV and -90 mV by changing the bicarbonate concentration in the medium or by voltage clamping. To avoid any interference by the inserted electrodes with the fluorescence measurement of the cytoplasm, the cells were fused by polyethyleneglycol to form giant cells (homokaryons). These homokaryons also allowed penetration by two glass microelectrodes without causing a serious leakage of the plasma membrane. The slow responding dye diBA-C4-(3)- had a fluorescence response of about 1% per mV. Mathematical analysis of the fluorescence changes after voltage clamping revealed a first-order reaction with a rate constant between 0.1 min-1 and 0.8 min-1, depending on the cell size which was determined by the number of nuclei per homokaryon. A model for the mechanism of the fluorescence changes is proposed.

Animals↗
PubMed1982

Closing and opening of gap junction pores between two- and three dimensionally cultured tumor cells.

Intercellular signal transfer via gap junction pores in cultured multicell spheroids of BICR/M1R-K cells decreases with increasing spheroid age. In two days old spheroids the pores allow passage of Lucifer yellow molecules. Two days later, this fluorescent dye is retained in the injected cell even though the cells are still electrically coupled. Gap junction plaques of considerable size are still found in 9 days old spheroids, when the cells are completely uncoupled. The same cells growing as monolayer cultures do not exhibit such a gradual closing of their gap junction pores: Their coupling is established at first cell contact, probably by a gradual opening of the pores, which remain open even up to 9 days in culture.

Animals↗
PubMed1978

Electronmicroscopical and electrophysiological investigations on polyethylene glycol induced cell fusion.

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.

Cell Fusion↗
PubMed1976

Electrophysiological properties of ethylnitrosourea-induced, neoplastic neurogenic rat cell lines cultured in vitro and in vivo.

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/M1RK, 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 N-ethyl-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.

Animals↗