scholarly journals Mitotic non-disjunction as a mechanism for in vitro aneuploidy induction by X-rays in primary human cells

Mutagenesis ◽  
1996 ◽  
Vol 11 (4) ◽  
pp. 307-313 ◽  
Author(s):  
M. Kirsch-Volders ◽  
I. Tallon ◽  
C. Tanzarella ◽  
A. Sgura ◽  
T. Hermine ◽  
...  
2019 ◽  
Author(s):  
Celia Lujan ◽  
Eleanor J. Tyler ◽  
Simone Ecker ◽  
Amy P. Webster ◽  
Eleanor R. Stead ◽  
...  

AbstractWe aim to improve anti-ageing drug discovery, currently achieved through laborious and lengthy longevity analysis. Recent studies demonstrated that the most accurate molecular method to measure human age is based on CpG methylation profiles, as exemplified by several epigenetics clocks that can accurately predict an individual’s age. Here, we developed CellAgeClock, a new epigenetic clock that measures subtle ageing changes in primary human cells in vitro. As such, it provides a unique tool to measure effects of relatively short pharmacological treatments on ageing. We validated the CellAgeClock against known longevity drugs such as rapamycin and trametinib. Moreover, we uncovered novel anti-ageing drugs, torin2 and Dactolisib (BEZ-235), demonstrating the value of our approach as a screening and discovery platform for anti-ageing strategies. The CellAgeClock outperforms other epigenetic clocks in measuring subtle ageing changes in primary human cells in culture. The tested drug treatments reduced senescence and other ageing markers, further consolidating our approach as a screening platform. Finally, we show that the novel anti-ageing drugs we uncovered in vitro, indeed increased longevity in vivo. Our method expands the scope of CpG methylation profiling from measuring human chronological and biological age from human samples in years, to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, providing a novel accelerated discovery platform to test sought after geroprotectors.


2019 ◽  
Vol 4 (1) ◽  
pp. e000217 ◽  
Author(s):  
Yoshimi Niwano ◽  
Atsuo Iwasawa ◽  
Kazuo Tsubota ◽  
Masahiko Ayaki ◽  
Kazuno Negishi

ObjectiveBlue light hazards for retina and ocular surface have been repeatedly described and many protective methods are introduced for retina; however, no study has been conducted on ocular surface protection. The purpose of this in vitro study was to examine phototoxicity and shade protection after blue light irradiation in primary human cells of corneal surface origin.Methods and analysisPrimary human cells of corneal surface origin were obtained from eye bank eyes. After blue light irradiation (405 nm) of these cells for 3 min, and a further 24 hours’ incubation, surviving viable cells were assessed by the methyl thiazolyl tetrazolium assay. Simultaneously, cell viability was determined in wells covered by ultraviolet and blue light shades.ResultsUnder subconfluent conditions, viable cells decreased by around 50% after blue light irradiation, compared with control cells without irradiation. The blue light phototoxicity was not blocked by the control shade, but the ultraviolet-blocking and blue light-blocking shades protected the cells from phototoxicity, producing a 30%–40% reduction (ultraviolet) and 15%–30% reduction (blue light) in viable cells.ConclusionThese results indicate that blue light injures ocular surface cells and the cells are protected from damage by a shade. We recommend blue light protection to maintain ocular health, especially in high-risk populations, such as people with dry eye, contact lens users, the malnourished and the elderly.


2019 ◽  
Vol 235 ◽  
pp. 415-423 ◽  
Author(s):  
Amy M. Zimmermann-Klemd ◽  
Viktoria Konradi ◽  
Carmen Steinborn ◽  
Annekathrin Ücker ◽  
Chiara Madlen Falanga ◽  
...  

2020 ◽  
pp. 1-20
Author(s):  
Rachel Verdon ◽  
Suzanne L. Gillies ◽  
David M. Brown ◽  
Theodore Henry ◽  
Lang Tran ◽  
...  

1957 ◽  
Vol 106 (4) ◽  
pp. 485-500 ◽  
Author(s):  
Theodore T. Puck ◽  
Dimitry Morkovin ◽  
Philip I. Marcus ◽  
Steven J. Cieciura

Survival curves of normal human cells from a variety of tissues exposed to varying doses of x-irradiation have been constructed, which permit definition of the intrinsic radiation sensitivity of the reproductive power of each cell type. The mean lethal dose of x-irradiation for all the cells employed, including those from normal and cancerous organs, those exhibiting diploid and polyploid chromosome number; those from embryonic and adult tissues, including recently isolated cells and cultures which had been maintained in vitro for many years, and cells exhibiting either epithelioid or fibroblastic morphology, was found to be contained between the limits of 50 to 150 r. Other similarities in the pattern of radiation effects, such as giant formation and abortive colonial growth, in these cells and that of the HeLa S3, previously studied, confirm the hypothesis that the pattern of reaction to x-irradiation previously elucidated, is representatative, at least in over-all outline, for a large variety of human cells. While the radiation survival curves of various human cells are similar in the gross, small but important characterizing differences have been found. All epithelioid cells so far studied are approximately 2-hit, and more radioresistant than the fibroblast-like cells whose survival data correspond to a mean lethal dose of around 60 r, and which so far can be fitted by either 1-hit or 2-hit curves. The earlier prediction that the major radiobiologic damage to mammalian cells is lodged in the genetic apparatus was confirmed by the demonstration of high frequency of mutants among the survivors of doses of 500 to 900 r. All the data on the x-radiosensitivity of these cells can be explained on the basis of a defect resulting from primary damage localized in one or more chromosomes. These considerations afford a convincing explanation of several aspects of the mammalian radiation syndrome.


Lab on a Chip ◽  
2019 ◽  
Vol 19 (21) ◽  
pp. 3697-3705 ◽  
Author(s):  
Patrick H. McMinn ◽  
Laurel E. Hind ◽  
Anna Huttenlocher ◽  
David J. Beebe

Her we report a new microfluidic technology designed to facilitate the study of neutrophil trafficking and priming using primary human cells with a high degree of spatiotemporal control.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Allison M. Khoo ◽  
Sang Hyun Cho ◽  
Francisco J. Reynoso ◽  
Maureen Aliru ◽  
Kathryn Aziz ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document