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W Scheid

Publications and source records attributed to W Scheid.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Calcium antagonists as amplifiers of the mutagenicity of cytostatic drugs].

Some calcium antagonists enhance synergistically the mutagenic efficiency of cytostatics. The results so far obtained concerning this phenomenon are described and discussed: (1) chromosome aberrations induced (in vitro) in human lymphocytes (cytostatics; bleomycin and peplomycin; calcium antagonists: verapamil and fendiline), (2) chromosome and chromatid aberrations induced (in vitro) in Chinese hamster ovary (CHO) cells (cytostatic: mitomycin C; calcium antagonist: verapamil), (3) gene mutations induced in the bacterium Salmonella typhimurium (cytostatics: mainly various anilinoacridine drugs; calcium antagonist: verapamil). In all 3 studies neither verapamil nor fendiline proved to be mutagenic when applied alone. The "comutagenicity" of calcium antagonists is compared with the enhancement of the cytotoxic (cell killing) efficiency of cytostatics by calcium antagonists. Both phenomena--potentiation of mutagenicity and of cytotoxicity--are interpreted on the basis of the "accumulation hypothesis". According to this hypothesis those calcium antagonists would enhance the mutagenic and cytotoxic efficiency of the cytostatics by inhibiting their extrusion from the cell. Consequently, the cytostatics would be accumulated in the cell and this would increase their mutagenic and cytotoxic efficiency. Since not all calcium antagonists investigated so far enhance the mutagenicity and cytotoxicity of cytostatics, this potentiation seems not to be caused by their calcium antagonistic action per se. Molecular, evolutionary, and medical aspects of the "accumulation hypothesis" are shortly discussed.

Animals↗
PubMed1992

Time-saving in biological dosimetry by using the automatic metaphase finder Metafer2.

The amount of time-saving by using the Metafer2 metaphase finder for routine analysis of radiation-induced chromosome aberrations (biological dosimetry) was determined. Metaphases were prepared by standard methods from cultures of human peripheral blood lymphocytes and stained either with Giemsa or with the FPG method. The metaphase finder was used for detecting metaphases on the microscope slides and for automatically processing the evaluation data. In our laboratory, standardized analysis of 1000 metaphases requires at least 3 working days for cell culturing and slide preparation and 51.5 working hours for cytogenetic analysis. When using the metaphase finder the time required for cytogenetic analysis is reduced to 17.3 working hours (time-saving factor: 51.5/17.3 h = 3.0). In our prolonged method, including more than one scoring of each slide and karyotyping of metaphases with chromosome aberrations, the analysis times for 1000 cells are 132 and 70 working hours, respectively (time saving factor: 132/70 h = 1.9).

Automation↗
PubMed1992

Significance testing in mutagen screening: the dependence of statistical power on the control sample size.

The continuous accumulation of control data in multicellular mutagen screening systems prompted us to study the dependence of the statistical power on the size of the control sample (for fixed control values). Two widely used screening systems were chosen: dicentric chromosomes in human lymphocytes and recessive sex-linked lethals in Drosophila melanogaster. The power increases rapidly at first as the control sample size increases, then levels off at a few tens of thousands of control units tested and thereafter remains almost constant up to the historical control. The practical implications from our study are discussed.

Animals↗
PubMed1991

A model for testing the mutagenicity of excimer laser radiation in ophthalmology.

Because excimer laser radiation is applied more and more in therapeutic and refractive corneal surgery, the possibility of mutagenic side effects of this treatment should be considered. A mutagenicity model is presented approximating closely the ophthalmological conditions when mutagenic effects are studied: Heparinized human blood is filled into the anterior chamber of an enucleated cow eye. After irradiation of the cornea with the excimer laser, the blood is removed and whole blood cultures are set up. Lymphocytes are stimulated, fixed during metaphase, and scored for chromatid and chromosome aberrations. First results obtained with this model after 248 nm laser irradiation (500 J, 277 mJ/cm2, 10 or 20 Hz) revealed no mutagenic effects. However, when the blood was exposed under the same physical conditions in a quartz chamber (positive control), statistically highly significant increases of the yields of chromatid aberrations were observed.

Adult↗
PubMed1991

[Induction of chromosome aberrations in human lymphocytes as a model for evaluating the mutagenic effect of excimer laser irradiation in ophthalmology].

A model for testing the mutagenicity of excimer laser radiation in ophthalmology is presented. In contrast to other studies using cell monolayers, in our study with this model human peripheral lymphocytes (heparinized whole blood) are exposed to laser irradiation at different conditions. The possible mutagenicity of secondary radiation after exposure of the cornea is also considered. The heparinized blood is either injected into the anterior chamber of an enucleated bovine eye or filled into a quartz chamber (positive control). After irradiation the lymphocytes are stimulated and fixed during metaphase, after which the metaphases are scored for chromatid and chromosome aberrations. In the positive control group, exposure to 248 nm excimer laser radiation (500 J, 277 mJ/cm2, 10 and 20 Hz) was followed by a highly significant increase in the yield of chromatid aberrations (chromatid breaks and achromatic lesions).

Animals↗
PubMed1991

Enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil and fendiline.

The enhancement of the mutagenicity of anticancer drugs by the calcium antagonists verapamil (CAS 52-53-9) and fendiline (CAS 13042-18-7) is reviewed. Both calcium antagonists enhance synergistically the induction of chromosome aberrations (dicentric and ring chromosomes) in cultured human lymphocytes by the antitumor agent bleomycin. Since two other calcium antagonists, nifedipine and diltiazem, when tested with the same system, did not show this effect, the comutagenicity of verapamil and fendiline does not seem to be related with calcium antagonism per se. Verapamil furthermore potentiates the induction of various chromosome and chromatid aberrations in Chinese hamster ovary (CHO) cells in vitro by the antitumor agent mitomycin C. In bacteria (Salmonella typhimurium) verapamil enhances synergistically the induction of gene mutations (frameshifts) by several anticancer drugs, including various anilinoacridine derivatives. When applied alone, neither verapamil which was tested in each of the three studies (human lymphocytes, CHO-cells, and bacteria) nor fendiline, which was tested only in human lymphocytes, proved to be mutagenic. To explain the comutagenicity of verapamil and fendiline, it is assumed that they prevent the mutagen (e.g., bleomycin) to be extruded from the cell. Consequently, the mutagen would be accumulated intracellularly and this would enhance its efficiency.

Animals↗