Mammalian in vivo cytogenetic assays. Analysis of chromosome aberrations in bone marrow cells.
About: This article is published in Mutation Research.The article was published on 1987-10-01. It has received 479 citations till now. The article focuses on the topics: Bone marrow & In vivo.
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TL;DR: A good correlation between the in vitro and in vivo experiments indicated that the biological applications employing Ag-np should be given special attention besides adapting the antimicrobial potential.
Abstract: The biocidal effect of silver nanoparticles (Ag-np) has resulted in their incorporation into consumer products. While the population exposed to Ag-np continues to increase with ever new applications, Ag-np remains a controversial research area with regard to their toxicity in biological systems. Here a genotoxic and cytotoxic approach was employed to elucidate the activity of Ag-np in vitro and in vivo. Characterization of Ag-np using scanning electron microscopy revealed a size range of 90-180nm. Cytotoxic potential of Ag-np was evaluated in human lymphocytes via cell viability assay (Trypan blue dye exclusion method, MTT and WST assay). The uptake and incorporation of Ag-np into the lymphocytes was confirmed by flow cytometry. Additionally apoptosis (AnnexinV-FITC-PI staining) and DNA strand breaks (comet assay) in human lymphocytes revealed that Ag-np at concentration 25μg/ml can cause genotoxicity. In vivo experiments on plants (Allium cepa and Nicotiana tabacum) and animal (Swiss albino male mice) showed impairment of nuclear DNA. Induction of oxidative stress was also studied. The DNA damage and chromosomal aberrations raise the concern about the safety associated with applications of the Ag-np. A single ip administration of Ag-np gave a significant (P≤0.05) increase in the frequency of aberrant cells and Tail DNA percent at concentrations 10mg/kg body weight and above. Results of comet assay in A. cepa and N. tabacum demonstrated that the genotoxic effect of Ag-np was more pronounced in root than shoot/leaf of the plants. The present study indicated a good correlation between the in vitro and in vivo experiments. Therefore the biological applications employing Ag-np should be given special attention besides adapting the antimicrobial potential.
192 citations
TL;DR: This review summarizes recent developments in the synthesis, characterization and biological activity of α-aminophosphonic acid and N-analogues and indicates one of the potential future developments is peptide hydrolysis.
Abstract: Aminophosphonic acids are an important group of medicinal compounds, and their synthesis has been a focus of considerable attention in synthetic organic chemistry as well as medicinal chemistry. Although the phosphonic and carboxylic acid groups differ considerably with respect to shape, size, and acidity, α-aminophosphonic acids are considered to be structural analogues of the corresponding amino acids and the transition state mimics peptide hydrolysis. This review summarizes recent developments in the synthesis, characterization and biological activity of α-aminophosphonic acid and N-analogues. An account of both uses will be presented, emphasizing one of the potential future developments, and some implications in medicinal chemistry are also disclosed. In addition, a brief account on the characterization of N-(phosphonomethyl) glycine derivatives will be presented.
168 citations
Cites background from "Mammalian in vivo cytogenetic assay..."
...…of a chemotherapeutic agent and anticancer compound was selected from the group consisting of N-(phosphonomethyl) glycine derivatives (Rueppel et al. 1977; Grossbard and Atkinson 1985; Tomlin 1997; Amrhein et al. 1980; Haslam 1974; Franz et al. 1997; Preston et al. 1987; Meek and Villafranca 1980)....
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TL;DR: No statistically significant alterations were found, as compared to untreated controls, in either the cell cycle or the number of chromosome alterations, after treatments with either plant, in rat cells or in cultured human lymphocytes.
Abstract: The use of medicinal plants by the general population is an old and still widespread practice, which makes studies of their genotoxicity essential. Psidium guajava L. and Achillea millefolium L. are examples of plants commonly used in popular medicine. P. guajava L. is indicated for diarrhea and also as an antiseptic, while A. millefolium L. is indicated as an analgesic, antispasmodic, digestive, diuretic, antiseptic, astringent, emollient, wound healer and hemorrhoid medication. The aim of this study was to determine the effects of the infusions of these two plant species on chromosomes and the cell cycle. Leaves from the plants were used to prepare infusions, in the same manner as teas, but at two different concentrations. Allium cepa L. root-tip cells (P. guajava L. - 2.62 and 26.2 mg/mL, and A. millefolium L. - 3.5 and 35.0 mg/mL) and Wistar rat bone marrow cells (P. guajava L. - 2.62 and 26.2 mg/100g body weight, and A. millefolium L. - 3.5 and 35.0 mg/100g body weight) were used as in vivo plant and animal test systems, respectively. Human peripheral blood lymphocytes (P. guajava L. - 0.262 and 2.62 mg/mL culture medium, and A. millefolium L. - 0.35 and 3.5 mg/mL culture medium) were used as in vitro test system. The P. guajava L. infusion at the higher concentration caused a statistically significant inhibition of cellular division in the onion root-tip cells, not observed in onion root-tip cells treated with A. millefolium L. No statistically significant alterations were found, as compared to untreated controls, in either the cell cycle or the number of chromosome alterations, after treatments with either plant, in rat cells or in cultured human lymphocytes. These results regarding the cytotoxicity and mutagenicity of these plants provide valuable information about the safety of using them as therapeutic agents.
145 citations
Cites methods from "Mammalian in vivo cytogenetic assay..."
...Bone marrow cells were obtained from the rats using the technique described by Ford and Hamerton (1956) and Preston et al. (1981; 1987a)....
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...Macrocultures of peripheral human blood lympho- cytes were prepared according to Moorhead et al. (1960) and Preston et al. (1981, 1987b), and used to determine the frequency and distribution of chromosome alterations....
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TL;DR: The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds.
127 citations
Cites background from "Mammalian in vivo cytogenetic assay..."
...The mammalian bone marrow chromosome aberration test (OECD 475; Adler, 1984; Preston et al., 1987 ) is an in vivo form of the previous in vitro test....
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TL;DR: It is concluded that pre-treatment with astaxanthin attenuates cyclophosphamide-induced oxidative stress and subsequent DNA damage in mice and it can be used as a chemoprotective agent against the toxicity of anticancer drug cycloph phosphamide.
125 citations
References
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TL;DR: A detailed survey is given of the types and classification of primary structural changes that can be induced in chromosomes and observed at the first metaphase after the initial damage.
Abstract: A detailed survey is given of the types and classification of primary structural changes that can be induced in chromosomes and observed at the first metaphase after the initial damage. Comments upon identification and scoring are given for the benefit of new workers. The annotation concludes with a brief discussion of the potential relationships between the primary types, and the secondary or derived types encountered in clinical studies.
501 citations
TL;DR: In this paper, a trend test for evidence of a dose response is proposed for such SCE data, where the percent of cells with chromosome aberrations is the response of interest, and Monte Carlo methods are used to show that the trend test is more sensitive than four other statistical procedures considered for the analysis of Poisson-distributed SCE.
Abstract: It is a widely held view that objective statistical criteria are needed for the evaluation of genetic toxicity assays. This paper presents statistical methods for the analysis of data from in vitro sister chromatid exchange (SCE) and chromosome aberration tests that use Chinese hamster ovary cells. For SCEs, an extensive study of solvent control results demonstrated that there is a substantial interday component of variability in the data, and that a Poisson sampling model is applicable to data generated via the protocol of Galloway et al [1985]. Consequently, a trend test for evidence of a dose response is proposed for such SCE data. As an illustration of this statistical method, analysis of data previously considered to be negative [Gulati et al, 1985] indicates that di(2-ethyl-hexyl) phthalate induces a weak, but reproducible, SCE dose response in CHO cells. Monte Carlo methods are used to show that the trend test is more sensitive than four other statistical procedures considered for the analysis of Poisson-distributed SCEs. A similar trend test for dose response in proportions is proposed for chromosome aberration data, where the percent of cells with chromosome aberrations is the response of interest. Sensitivity (or power) studies indicate that three doses and a control with 50 cells/dose point is a reasonable design for an in vitro SCE study that uses the Galloway et al protocol. For in vitro chromosome aberrations, however, three doses and a control with 100 cells/dose point appears to produce too insensitive an assay; an increase to 200 cells/dose point in the Galloway et al protocol seems worthy of serious consideration.
157 citations