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Journal ArticleDOI

Frequency of sister chromatid exchanges induced by trimethyltin chloride in human peripheral blood lymphocytes as related to age of donors. A brief report.

01 Oct 1989-Mechanisms of Ageing and Development (Elsevier)-Vol. 50, Iss: 1, pp 95-102
TL;DR: Two concentrations (0.5 microgram and 1.0 microgram) of trimethyltin chloride were added to lymphocytes of healthy male and female donors of different age groups and cultured at 37 degrees C for 72 h and the range and mean number of sister chromatid exchanges were significantly increased.
About: This article is published in Mechanisms of Ageing and Development.The article was published on 1989-10-01. It has received 14 citations till now. The article focuses on the topics: Sister chromatid exchange & Trimethyltin chloride.
Citations
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Journal ArticleDOI
TL;DR: The general hypothesis that aging and longevity are the result of a balance between mechanisms that favor aging and mechanisms that counteract the aging is proposed.
Abstract: In previous papers we proposed the general hypothesis that aging and longevity are the result of a balance between mechanisms that favor aging and mechanisms that counteract the aging The mechanisms favoring aging and senescence are those that cause damage to macromolecules and other body components. They come from both exogenous and endogenous sources. Ionizing radiation, UV radiation, and xenobiotics, including dietary carcinogens, are the most common exogenous genotoxic compounds with which we cope in everyday life. Body heat, oxygen free radicals, glucose, and other oxidative sugars are representative of the byproducts of a variety of metabolic pathways and represent unavoidable, potentially genotoxic agents3

73 citations

Journal ArticleDOI
TL;DR: Human peripheral blood lymphocytes of healthy male and female individuals of different age groups were treated with two aqueous doses of trimethyltin chloride and Chromatid and chromosome types of aberrations were observed to be increased in both treated sets in all age groups.

33 citations

Journal ArticleDOI
TL;DR: The clastogenicity of trimethyltin chloride was evaluated in human peripheral blood lymphocytes with micronucleus counts (MNC) as the endpoint and higher frequencies of MNC enhancement were observed in male individuals than in females.

32 citations

Journal ArticleDOI
TL;DR: The comparative effects of inorganic and organic tin compounds on chromosomes were assessed in human peripheral blood lymphocytes of healthy donors 20-40 years of age and the endpoints observed were chromosomal abnormalities, sister-chromatid exchanges (SCEs) and cell cycle kinetics.

25 citations

Dissertation
26 Jan 2005
TL;DR: In this paper, the authors investigated the toxicity of arsenic compounds in terms of cytotoxicity and DNA damage, and found that the cytotoxic effects were dose-dependent and inhibited at higher doses.
Abstract: Metals and metalloids are transformed naturally in the environment with formation of volatile and non-volatile organic derivatives. This process has a major role in metals mobility and accumulation in biological systems. Thus, considerable amounts of metallic and organometallic species are also introduced into the environment, causing concern about their impact on human’s health. In addition, arsenic species and organotin are also produced as a result of human intracellular metabolism. The aim of the study is to investigate the toxic potential that can lead to cell death of organometal(loid)s. Here, cyto- and genotoxic effects in relationship with cellular uptake; disturbed calcium homeostasis in relationship with cell death of arsenic compounds (inorganic arsenic: Asi(V), Asi(III) and their methylated metabolites: MMA(V), MMA(III), DMA(V), DMA(III) and TMAO(V)), organoantimony (TMSb(V)), and organotin compounds (MMT, DMT, TMT, TetraMT) were investigated in mammalian cells (CHO-9, HeLa S3, and Hep G2 cells), in vitro. These compounds showed different levels of cytotoxic effects. Thus, the DNA damage induced by the mentioned compounds was low or recovered (DNA repair). The uptake was dose-dependent, but low membrane permeability was observed. For arsenic, the uptake was higher with lower doses and inhibited at higher doses. Hep G2 cells had the highest cellular uptake as compared with CHO and HeLa cells. These compounds were not attached at cell plasma membranes. When cellular uptake was increased, a significant genetic damage was observed. In addition, because cytosolic calcium is a universal messenger mediating physiological and pathological cell functions, its modulation by the mentioned organometallic species were investigated. Trivalent arsenic species are the most active toxic forms inducing cytotoxicity and DNA damage. These arsenic forms were taken up by the cells faster compared to pentavalent species. Pentavalent organic arsenic forms did not show high toxic effects under normal experimental conditions but they exhibit genotoxic effects after forced uptake. Arsenic compounds perturbed calcium homeostasis but the effect was reversible. To compare, TMSb was more potent than its arsenic equivalent in cytotoxic abilities and induced DNA damage under forced uptake. Also, it was able to increase intracellular calcium and trigger cell death (apoptosis). In addition, the ability of organotin compounds to penetrate cell membranes modulates their genotoxicity but not the induced cytotoxic effects. They induced significant DNA damage and high cytotoxicity in forced uptake. Also, TMT (0.25 µM to 500 µM) triggered cell signalling in HeLa cells. Calcium rise was reversible, repeatable, and dose-dependent in regards to the reactive cells and the increase in intracellular calcium. This elevation derived principally from internal stores because it did not depend on the extracellular calcium concentration and was extremely diminished after treatment of caffeine. An increase in the calcium concentration in the nuclear region of HeLa cells (after TMT addition) was also observed. Calcium signalling patterns occurred as spikes, and sustained plateau. Since it is not clear whether fast calcium changes contribute to the efficiency or specificity of signalling, or are a consequence of the feedback control of Ca2+, the relationship of Ca2+ changes and cellular death (necrosis or apoptosis) was investigated. At low concentrations, TMT was able to induce significant apoptotic death. Additionally, all other organotin compounds were able to modulate calcium homeostasis and trigger apoptosis.

17 citations

References
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Journal ArticleDOI
13 Nov 1975-Nature
TL;DR: A staining technique that detects sister chromatid exchanges (SCEs) has been used to examine the response of chromosomes in cultured Chinese hamster cells to a wide variety of mutagens–carcinogens.
Abstract: A staining technique that detects sister chromatid exchanges (SCEs) has been used to examine the response of chromosomes in cultured Chinese hamster cells to a wide variety of mutagens-carcinogens. The test gives a very sensitive and rapid method for detecting chromosome mutagenicity of chemical agents and provides a powerful new method for detecting environmental mutagens.

1,306 citations

Journal ArticleDOI
TL;DR: Chinese hamster ovary cells grown for two rounds of DNA replication in the presence of BrdUrd contain sister chromatids that fluoresce differentially when stained with Hoechst 33258, and the staining patterns obtained in endoreduplicated cells clearly confirm that the polynucleotide strands of the DNA segregate into sister Chromatids as though the newly synthesized strands were laid on the outside of the replicating double helix.
Abstract: Chinese hamster ovary cells grown for two rounds of DNA replication in the presence of BrdUrd contain sister chromatids that fluoresce differentially when stained with Hoechst 33258. If such fluorescent treatments are followed by incubation in 2 X SSC or water at 62° C and staining in 3% Giemsa, the chromosomes now contain one dark (unifilarly substituted) chromatid and one light (bifilarly substituted) chromatid, i.e. are “harlequinized”. These preparations do not fade and can be studied without resorting to fluorescence microscopy. Sister chromatid exchanges (SCE's) are seen with great clarity and resolution; and all the chromosomes in a cell can be scored, which is contrary to the usual experience with autoradiography. It was found that a) the yield of SCE's is dependent upon the concentration of BrdUrd in which the cells are grown and that the maximum number of SCE's that can occur spontaneously is 0.15 per chromosome per division cycle, b) the yield of SCE's doubles if the cells are exposed to visible light that can cause the photolysis of BrdUrd-containing DNA, and c) chromosomes that appear isolabelled in autoradiographic preparations come from observable multiple exchanges and are not the result of the segregation of DNA from a binemic chromosome. Furthermore, the staining patterns obtained in endoreduplicated cells clearly confirm that the polynucleotide strands of the DNA segregate into sister chromatids as though the newly synthesized strands were laid on the outside of the replicating double helix.

565 citations

Journal ArticleDOI
TL;DR: A total of 174 test agents, including pharmaceuticals, food additives, pesticides and organic extracts of air and water pollutants, was tested for mutagenicity in mice using the modified dominant lethal assay, with results determined by increased early fetal deaths per pregnancy and, in some instances, also indirectly by reduction in total implants per pregnancy.

454 citations

Journal ArticleDOI
TL;DR: Failure of the pale stained chromatids to restore Giemsa affinity with urea and trypsin and the diminished Feulgen reaction after light exposure suggest that not masking proteins but photolysis of the BrdU-incorporated chromatid components in the presence of photosensitive dyes play a role in the differential staining.
Abstract: The essential steps of the 33258 Hoechst-Giemsa method for differential chromatid staining consist of (1) 33258 Hoechst treatment, (2) exposure to light, and (3) Giemsa staining. The staining was shown to be a function of the concentration of 33258 Hoechst and the light exposure. The dye was successfully replaced by various metachromatic dyes such as thionine. Two simple methods are proposed. Failure of the pale stained chromatids to restore Giemsa affinity with urea and trypsin and the diminished Feulgen reaction after light exposure suggest that not masking proteins but photolysis of the BrdU-incorporation chromatid components in the present of photosensitive dyes play a role in the differential staining.

280 citations