Cellular transition to senescence is associated with extensive chromatin reorganization and changes in gene expression. Recent studies appear to imply an association of lamin B1 (LB1) reduction with chromatin rearrangement in human fibroblasts promoted to senescence, while the mechanisms and structural features of these relationships have not yet been clarified. In this work, we examined the functions of LB1 and the lamin B receptor (LBR) in human cancer cells. We found that both LB1 and LBR tend to deplete during cancer cell transfer to senescence by γ-irradiation. A functional study employing silencing of LBR by small hairpin ribonucleic acid (shRNA) constructs revealed reduced LB1 levels suggesting that the regulation of both proteins is interrelated. The reduced expression of LBR resulted in the relocation of centromeric heterochromatin (CSH) from the inner nuclear membrane (INM) to the nucleoplasm and is associated with its unfolding. This indicates that LBR tethers heterochromatin to INM in cycling cancer cells and that LB1 is an integral part of this tethering. Down-regulation of LBR and LB1 at the onset of senescence are thus necessary for the release of heterochromatin binding to lamina, resulting in changes in chromatin architecture and gene expression. However, the senescence phenotype was not manifested in cell lines with reduced LBR and LB1 expression suggesting that other factors, such as deoxyribonucleic acid (DNA) damage, are needed to trigger senescence. We conclude that the primary response of cells to various stresses leading to senescence consists of the down-regulation of LBR and LB1 to attain reversal of the chromatin architecture.
- MeSH
- centromera metabolismus účinky záření ultrastruktura MeSH
- heterochromatin metabolismus účinky záření ultrastruktura MeSH
- jaderný obal metabolismus účinky záření ultrastruktura MeSH
- lamin typ B genetika metabolismus MeSH
- lidé MeSH
- malá interferující RNA genetika metabolismus MeSH
- MFC-7 buňky MeSH
- nádorové buněčné linie MeSH
- osteoblasty metabolismus patologie účinky záření MeSH
- receptory cytoplazmatické a nukleární antagonisté a inhibitory genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- signální transdukce MeSH
- stárnutí buněk účinky záření MeSH
- záření gama MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To assess the radiation exposure of radon spa personnel in Jáchymov, Czech Republic. METHODS: The frequency of micronucleus-containing cells and the percentage of centromere-free micronuclei (micronuclei containing only acentric fragments) was determined in peripheral blood lymphocytes of 42 individuals working at the Jáchymov spa and 42 control individuals. RESULTS: There was a highly significant increase in the frequency of micronucleus-containing cells as well as the percentage of centromere-free micronuclei in the lymphocytes of spa personnel versus controls. No individual dosimetry data were available. A comparison with results from currently active uranium miners suggests that the individuals examined at the Jáchymov spa had accumulated effective doses in the order of several tens of mSv, very similar to those of the miners. CONCLUSION: The spa personnel in Jáchymov needs to be monitored on an individual level.
- MeSH
- centromera genetika účinky záření MeSH
- dospělí MeSH
- hornictví MeSH
- lázně * MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty patologie účinky záření MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní * MeSH
- monitorování životního prostředí MeSH
- pracovní expozice škodlivé účinky analýza MeSH
- radon * škodlivé účinky MeSH
- senioři MeSH
- uran * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
Micronuclei can be used as markers of past radiation exposure, but only few studies have dealt with uranium miners. In this paper, we report on micronuclei in lymphocytes from individuals currently working at Rožná, Czech Republic, the last functioning uranium mine in the European Union. A modified micronucleus-centromere test was applied to assess the occurrence of micronuclei in stimulated lymphocytes, as well as their content in terms of whole chromosomes or fragments. Compared with unexposed individuals, the miners had higher frequencies of micronucleus-containing lymphocytes and higher percentages of micronuclei without centromeres, and the differences were significant for both parameters (0.74 ± 0.60 vs. 0.50 ± 0.42, p = 0.017 and 49 ± 44 vs. 12 ± 21, p = 0.0002; means ± standard deviations). There were also significant correlations between one or other of these parameters on the one hand and various dose values on the other, in particular with a 'retrievable' dose, that is, a dose whose effect should still be recognisable in lymphocytes assuming a half-life of 3 years. The 'retrievable' dose at which a doubling of the micronucleus frequency was observed was around 35 mSv, corresponding to a total dose of 90 mSv received while working in the mines. Altogether, our data show that the micronucleus-centromere test is a valuable tool for the assessment of past radiation exposure in uranium miners. The scatter in the data is of course far too great to allow individual dosimetry, but for groups of a few dozen exposed individuals, the method can be used to monitor doses clearly below 100 mSv.
- MeSH
- centromera genetika účinky záření MeSH
- hornictví * MeSH
- lidé MeSH
- lymfocyty patologie účinky záření MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní účinky záření MeSH
- pracovní expozice škodlivé účinky analýza MeSH
- uran škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
Micronuclei can be used as markers of past radiation exposure, but few pertinent studies have dealt with alpha radiation. Here we report on micronuclei in lymphocytes from uranium miners, comparing some that are currently active and others that retired 15-20 years ago. Their radiation exposure is assumed to come mainly from radon and its decay products in the air breathed at the work place. Current miners showed a greater micronucleus frequency than former miners. This can be attributed to their recent radiation exposure, while the lower frequency in the former miners probably results from the disappearance of potentially micronucleus containing lymphocytes from the peripheral blood, which is known to occur with a half-life of about one year. For current miners there is a significant correlation between micronucleus frequency and effective dose received over the last 12 months. The dose at which a doubling of the micronucleus frequency is observed is around 10 mSv. This is a much smaller dose than would usually be expected to be detectable with this test, and raises a number of questions about the induction of micronuclei by alpha radiation from radon and its decay products.
- MeSH
- časové faktory MeSH
- centromera genetika účinky záření MeSH
- cytogenetické vyšetření MeSH
- dávka záření MeSH
- dospělí MeSH
- financování organizované MeSH
- krev účinky záření MeSH
- krevní buňky účinky záření MeSH
- kultivační techniky MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty cytologie účinky záření MeSH
- mikrojaderné testy metody MeSH
- mikrojádra chromozomálně defektní účinky záření MeSH
- pracovní expozice škodlivé účinky MeSH
- radiační účinky MeSH
- radon škodlivé účinky toxicita MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- uran škodlivé účinky toxicita MeSH
- věkové faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
