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[Effect of different cytostatic agents and antibiotics on the biology of Trichomonas in vitro].

The purpose of these examinations was an attempt to elucidate the influence of some cytostatic preparations (Fluorouracil, Triaziquone (Treminon), Mechlorethaminee Oxide Hydrochloride (Mitomen), Methotroxate, Mitomycins, Cyclophosphamide (Endoxan), Mechlorethamin (Nitrogranulogen) and antibiotics (Penicillin, Streptomycin, Aureomycin, Nystatin) on formation of the multinuclear forms of Trichomonas under the conditions of culture on artificial medium and to investigate the cidal and static effects of chosen cytostatics and antibiotics of different species of Trichomonas in vitro. It was found that Mechlorethamine (Nitrogranulogen) and Mitomycins have distinct influence on formation of the multinuclear forms of Trichomonas in culture. Similar effects were observed in the antibiotic group with aureomycin only if applied pure or combined with other antibiotic drugs. In addition, it was shown that Triaziquone (Treminon) exerts the strongest effects on the examined species of Trichomonas.

Anti-Bacterial Agents↗

Protection from cytotoxic effects induced by the nitrogen mustard mechlorethamine on human bronchial epithelial cells in vitro.

The present study was undertaken to find potent molecules against the toxicity of nitrogen mustard mechlorethamine (HN2) on respiratory epithelial cells, using a human bronchial epithelial cell line (16HBE14o-) as an in vitro model. The compounds examined included inhibitors of poly(ADP-ribose) polymerase (PARP), sulfhydryl-group donors as nucleophiles, and iron chelators and inhibitors of lipid peroxidation as antioxidants. Their effectiveness was determined upon observance of metabolic dysfunction induced by HN2 following a 4-h exposure, using (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction and ATP-level assays as indicators. Moreover, the fluorescent probe, monobromobimane (mBBr), and 2',7'-dichlorofluorescin-diacetate (H2DCF-DA) were used to assess intracellular sulfhydryl and peroxide level modifications by flow cytometry, respectively, following a 3-h exposure. At last, cell death was assessed by flow cytometry using the propidium iodide (PI)-dye-exclusion assay following 24-h exposure. PARP inhibitors (niacinamide, 3-aminobenzamide, 6(5H)-phenanthridinone), and two sulfhydryl-group donors (N-acetylcysteine, WR-1065) were found to be effective in preventing HN2-induced metabolic dysfunction when added in immediate or delayed treatment with HN2. Only N-acetylcysteine, however, was found to prevent cell death induced by HN2, though it must be present at the time of the HN2 challenge. Flow cytometric measurements of intracellular sulfhydryl levels strongly suggested that N-acetylcysteine and WR-1065 are preventive in alkylation of cellular compounds, mainly by direct extracellular interaction with HN2. PARP inhibitors prevent secondary deleterious effects induced by HN2, considering metabolism dysfunction as the endpoint. Elsewhere, the oxidative stress appears to be a side effect in HN2 toxicity only upon considering the inefficiency of several antioxidants.

Adenosine Triphosphate↗

Prophage inductive efficiency of alkylating agents and radiations.

The prophage inducing efficiency in E. coli K-12 (lambda) of a number of agents--alkylating agents and radiations--has been compared at a high survival of bacteria. The inducing effectiveness (per alkylation in DNA) and efficiency (compared with mutation frequency in E. coli Sd-4) was found to decrease in the order 2-hydroxyethylating agents (2-hydroxyethyl methanesulphonate and ethylene oxide) greater than isopropyl methanesulphonate approximately equal to methyl methanesulphonate greater than ethylating agents (diethyl sulphate, ethyl methanesulphonate). The low inducing activity of the ethylating agents could not be explained with respect to their reactivity towards targets of differing nucleophilicity, nor could the effectiveness in mutagenicity or the ability to break the chromosomes in the presence of metal ions be invoked. The high inducing efficiency of hydroxyalkylating agents may be related to their ability to break DNA strands.

Alkylating Agents↗