Search results for "Micronucleus Tests"
showing 10 items of 26 documents
In Vitro Assessment of the Genotoxic Hazard of Novel Hydroxamic Acid- and Benzamide-Type Histone Deacetylase Inhibitors (HDACi)
2020
Histone deacetylase inhibitors (HDACi) are already approved for the therapy of leukemias. Since they are also emerging candidate compounds for the treatment of non-malignant diseases, HDACi with a wide therapeutic window and low hazard potential are desirable. Here, we investigated a panel of 12 novel hydroxamic acid- and benzamide-type HDACi employing non-malignant V79 hamster cells as toxicology guideline-conform in vitro model. HDACi causing a &ge
Genomic instability induced by α-pinene in Chinese hamster cell line.
2012
Here, we report the effects of exposure of mammalian cells to α-pinene, a bicyclic monoterpene used in insecticides, solvents and perfumes. Morphological analysis, performed in V79-Cl3 cells exposed for 1 h to increasing concentrations (25 up to 50 μM) of α-pinene, indicated a statistically significant increase in micronucleated and multinucleated cell frequencies; apoptotic cells were seen at 40 and 50 μM. This monoterpene caused genomic instability by interfering with mitotic process; in fact, 50% of cells (versus 19% of control cells) showed irregular mitosis with multipolar or incorrectly localised spindles. Cytogenetic analysis demonstrated high-frequency hypodiploid metaphases as well…
DNA damage by bromate: Mechanism and consequences
2005
Abstract Exposure of mammalian cells to bromate (BrO3−) generates oxidative DNA modifications, in particular 7,8-dihydro-8-oxo-guanine (8-oxoG). The damaging mechanism is quite unique, since glutathione, which is protective against most oxidants and alkylating agents, mediates a metabolic activation, while bromate itself does not react directly with DNA. Neither enzymes nor transition metals are required as catalysts in the activation. The ultimate DNA damaging species has not yet been established, but experiments under cell-free conditions suggest that neither molecular bromine nor reactive oxygen species such as superoxide, hydrogen peroxide or singlet oxygen are involved. Rather bromine …
Expression of xenobiotic-metabolizing enzymes in propagatable cell cultures and induction of micronuclei by 13 compounds
1990
Activities of various xenobiotic-metabolizing enzymes were determined in 18 cell lines. Activities of cytochrome P450 reductase, microsomal epoxide hydrolase and glutathione transferase were detectable in all lines. The highest values were similar to the activities found in freshly isolated rat hepatocytes. Catalase activity was also present in all 12 investigated cell lines. Activity of UDP-glucuronosyl transferase was high in some lines, but low or undetectable in others. Activity of cytosolic epoxide hydrolase was not measurable in most lines, and was low in the others. Metabolism of benzo[a]pyrene was observed in eight out of nine examined lines, no activity being found in V79 cells. V7…
Fjord-region diol-epoxides of benzo[c]chrysene are potent inducers of micronuclei in murine bone marrow
1994
Abstract Vicinal diol-epoxides are the best established carcinogenic metabolites of polycyclic aromatic hydrocarbons. Numerous studies have demonstrated their high genotoxic activity in various in vitro test systems. However, in vivo mutagenicity data are not available. The fjor-region diol-epoxides of benzo[ c ]chrysene combine high mutagenic activity in vitro with hydrolytic stability. They were tested for the induction of micronuclei in the bone marrow following intraperitoneal administration to NMRI mice. The anti diasteromer of the diol-epixode enhanced the frequency of micronucleated polycrhomatic erythrocytes strongly (7–19-fold above the value in untreated controls) over a very wide…
Protective Effects of Fruits and Vegetables against In Vivo Clastogenicity of Cyclophosphamide or Benzo[a]pyrene in Mice
1998
Seven fruits and 10 vegetables commonly consumed in Germany were investigated for their anticlastogenic potencies against cyclophosphamide (CP) and benzo[a]pyrene (BaP) in the in vivo mouse bone marrow micronucleus assay. We detected protective effects in 76.5% and 70.6% of the samples, respectively, and more or less distinct quantitative differences between the various plant materials and the two clastogens investigated. With respect to CP, moderate activities were exerted by sweet cherries, strawberries, cucumber, radish and tomatoes, average activities by bananas, oranges, peaches, asparagus and red beets and strong activities by yellow red peppers and especially spinach. Apples (cultiva…
In vivo genotoxicity of selected herbicides in the mouse bone-marrow micronucleus test
1997
The herbicides alachlor, atrazine, terbuthylazine, gluphosinate-ammonium, isoproturon, pendimethaline and trifluralin were tested for genotoxicity in the mouse bone-marrow micronucleus test (MNT). Both atrazine and trifluraline caused a significant increase in the number of micronuclei at doses of 1,400 mg/kg body weight in female mice only. Alachlor, terbuthylazine, gluphosinate-ammonium, isoproturon and pendimethaline did not have any genotoxic effect in the mouse bone-marrow micronucleus test in either female or male animals.
Inhibition of clastogenicity of benzo[a]pyrene and of its trans-7,8-dihydrodiol in mice in vivo by fruits, vegetables, and flavonoids.
2003
In the in vivo mouse bone marrow micronucleus assay, homogenates of spinach, artichoke, peaches, and blue grapes as well as commercial concentrates of these vegetables and fruits reduced induction of micronuclei by benzo[a]pyrene (BaP) by 43-50%. Concentrates of strawberries (31% reduction) and of cauliflower (20% reduction) were less potent. Inhibition of genotoxicity by spinach and peaches was not caused by any delay in maturation of micronucleated erythrocytes as shown by experiments with sampling times of 24, 48, and 72 h after dosing of BaP. Pre-treatment of the mice with spinach 48, 24, and 12h before application of BaP resulted in a 44% reduction of micronuclei while peaches generate…
Stable expression of human cytochrome P450 1A1 cDNA in V79 Chinese hamster cells and metabolic activation of benzo[a]pyrene
1993
A V79 Chinese hamster cell line stably expressing human cytochrome P450 1A1 (CYP1A1) was obtained by chromosomal integration of the human CYP1A1 cDNA under the control of the SV40 early promoter. Chromosomal integration was verified by Southern analysis, and effective transcription of the human CYP1A1 cDNA was demonstrated by Northern analysis. The CYP1A1 cDNA-encoded protein was characterized by Western analysis using anti-rat CYP1A1. Intracellular association of CYP1A1 with the endoplasmic reticulum could be visualized by in situ immunofluorescence. Crude cell lysates of the V79 derived cell line was able to catalyze 7-ethoxyresorufin-O-deethylation (EROD) with an activity of about 50 pmo…
Visible light (>395nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers
2004
Solar radiation gives rise to DNA damage in mammalian cells not only directly by excitation of DNA, which generates predominantly pyrimidine dimers, but also indirectly by the excitation of endogenous photosensitizers, which causes oxidative DNA modifications. The latter mechanism has a low quantum yield, but it is the only one proceeding in the visible range of the spectrum. To investigate its relevance for the genotoxicity of sunlight, we have analysed the generation of micronuclei associated with the induction of oxidative DNA damage by visible light in melanoma cells and primary human skin fibroblasts. Similar yields of light-induced oxidative DNA base modifications sensitive to the rep…