Metallothionein in radiation exposure: its induction and protective role

Cai, Lu; Satoh, Masahiko; Tohyama, Chiharu; Cherian, M. George

doi:10.1016/s0300-483x(98)00150-4

Cited by 188 publications

(141 citation statements)

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“…It has been reported that MT-null mice and cells derived from them were more sensitive to the toxic effects of heavy metals such as cadmium (Klaassen et al, 1999), toxic agents such as hydrogen peroxide and tert-butyl hydroperoxide (Chubatsu and Meneghini, 1993;Schwarz et al, 1994), and radiation exposure (Cai et al, 1999) as compared to MT-wildtype and MT I-overexpressing mice. Cells pre-induced to express MT were also more resistant against the toxic effects of cadmium (Goering and Klaassen, 1984;Klaassen et al, 1999) and radiation exposure (Cai et al, 1999) as compared to control cells. In human T cell and breast carcinoma cell lines, down-regulation of MT with antisense MT oligomers not only inhibited growth of the cells, but also activated apoptosis (Abedel-Mageed and Agrawal, 1997;Tsangaris and Tzortzatou-Stathopoulou, 1998).…”

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confidence: 99%

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Fan

Cherian

2002

Br J Cancer

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The expression and induction of metallothionein has been associated with protection against oxidative stress and apoptosis. This study examines the effect of tumour suppressor protein p53 on metallothionein expression following CdCl 2 treatment in eight human epithelial breast cancer cell lines differing in p53 and oestrogen-receptor status. Cells were treated with 10 mM CdCl 2 for 24 h and metallothionein protein levels were measured by cadmium binding assay. MCF7 cells which are p53-positive (p53+) and oestrogen-receptor-positive showed a large induction in metallothionein synthesis by 10.79+1.36-fold. Other breast cancer cell lines which are p53-negative (p537) and oestrogen-receptor-negative or weakly oestrogenreceptor-positive showed a small induction ranging from 1.40+0.10 to 3.65+0.30-fold. RT -PCR analysis showed an induction of metallothionein mRNA in MCF7 cells by about 1.61+0.08-fold, while in HCC1806 cells (p537, oestrogenreceptor-negative) by 1.11+0.13-fold, and in MDA-MB-231 (p537, oestrogen-receptor-negative) by 1.25+0.06-fold. Metallothionein localisation was determined by immunohistochemical staining. Prior to metal treatment, metallothionein was localised mainly in the cytoplasm of MCF7 and MDA-MB-231 cells. After treatment with 10 mM CdCl 2 for 24 h, MCF7 cells showed intense nuclear and cytoplasmic staining for metallothionein, while MDA-MB-231 cells showed staining in the cytoplasm with weak nuclear staining. Apoptosis induced by 10 -40 mM CdCl 2 at time points between 4 and 48 h was examined with TUNEL assay. In MCF7 cells, apoptosis increased with higher concentrations of CdCl 2 , it peaked at 6 -8 h and appeared again at 48 h for all concentrations of CdCl 2 tested. In MDA-MB-231 cells, apoptosis remained at low levels for 10 -40 mM CdCl 2 at all time points. Studies on cadmium uptake showed similar uptake and accumulation of cadmium at 8 and 24 h in all the cell lines. The data demonstrate that treatment of epithelial breast cancer cells with 10 mM CdCl 2 for 24 h caused a greater induction of metallothionein protein and mRNA expression in p53+ and oestrogen-receptor-positive cells as compared to p537 and oestrogen-receptor-negative or weakly oestrogen-receptor-positive cells. This effect may be associated with the occurrence of apoptosis and suggests a role for p53 and oestrogen-receptor on the expression and induction of metallothionein in epithelial cells.

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confidence: 99%

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Fan

Cherian

2002

Br J Cancer

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“…The sensitivity of mitochondria to adverse effects was also described in the snail L. stagnalis (Masola et al, 2008) and bivalve molluscs (Ivanina et al, 2008). Among the studied biomarkers, low-molecular-weight intracellular thiols, MTs and GSH, that perform crucial biological functions involved in the general stress response, particularly scavenging of reactive oxygen species, and storage and transport of metal ions (Cai et al, 1999;Viarengo et al, 2007) were selected as important indices for the distinguishing of groups (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…3). Upregulation of these stress-related thiols is considered to be one of the mechanisms involved in the adaptive response to low-dose radiation exposure (Cai et al, 1999;Olsvik et al, 2010). On the other hand, the decreased level of GSH under the influence of low-level radiation (below 20 cSv), accompanied by increases in the level of lipid peroxidation products in human plasma was revealed long after the accident (4-7 years) in the liquidators and children of exposed mothers from the ChNPS area (Ivanenko et al, 2008).…”

Section: Resultsmentioning

confidence: 99%

“…The presence of MT in the cells may provide protective effects from radiationinduced genotoxicity and cytotoxicity (Cai et al, 1999). However, the main feature of the molluscs from the Chernobyl area was the depletion of MT: it was probably a result of the exhaustion of the stress-induced gene regulation.…”

Section: Resultsmentioning

confidence: 99%

“…This can probably be explained by the well-studied phenomenon termed radio-adaptation (Howell et al, 2011). At the same time, it is known that low doses of γ-irradiation in laboratory conditions induced significant upregulation of the stress-related genes in aquatic animals (Cai et al, 1999;Olsvik et al, 2010). Study in the Chernobyl Nuclear Power station (ChNPS) area is of particular interest regarding the necessity to understand the remaining consequences of the Chernobyl accident.…”

Section: Introductionmentioning

confidence: 99%

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Metallothionein and glutathione inLymnaea stagnalisdetermine the specificity of responses to the effects of ionising radiation

et al. 2012

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The aim of our study was to distinguish the stress-related molecular response of the pulmonate mollusc Lymnaea stagnalis from the Chernobyl area in comparison with the consequences of other harmful effects, including the short-term effects of radiation and heating. Specimens inhabiting ponds near the Chernobyl nuclear power plant, the cooling channel of the electric power station and the soilreclamation channel (groups R, T and C, correspondingly), and specimens adapted to laboratory conditions (a control group (CL), a disposable group exposed to 2 mGy X-ray radiation over the body (RL), and a group exposed to 25°C for 4 days (TL)) were compared. Despite high variability of responses, Principle Component Analysis distinctly separated the laboratory and feral groups into two sets. In the feral groups, low levels of the stress-related and metal-binding protein metallothionein (MT), protein carbonyls and lactate dehydrogenase in the digestive gland were indicated. The main separating criteria selected by classification and regression tree analysis were the protein carbonyls, cholinesterase and MT. Molluscs from group R were clearly distinguished by the lowest levels of MT, Mn-superoxide dismutase and lactate dehydrogenase, and the highest level of glutathione, demonstrating that the oppression of the gene-determined stress-related response and its partially metabolic compensation can be possible markers for chronic environmental effects of irradiation.

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2019

Industrial and Medical Nuclear Accidents

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Metallothionein in radiation exposure: its induction and protective role

Cited by 188 publications

References 69 publications

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Potential role of p53 on metallothionein induction in human epithelial breast cancer cells

Metallothionein and glutathione inLymnaea stagnalisdetermine the specificity of responses to the effects of ionising radiation

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