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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Evaluation of human embryonic stem cells and their differentiated fibroblastic progenies as cellular models for in vitro genotoxicity screening
Journal of Biotechnology, Volume 184, Year 2014
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Description
This study evaluated human embryonic stem cells (hESC) and their differentiated fibroblastic progenies as cellular models for genotoxicity screening. The DNA damage response of hESCs and their differentiated fibroblastic progenies were compared to a fibroblastic cell line (HEPM, CRL1486) and primary cultures of peripheral blood lymphocytes (PBL), upon exposure to Mitomycin C, gamma irradiation and H2O2. It was demonstrated that hESC-derived fibroblastic progenies (H1F) displayed significantly higher chromosomal aberrations, micronuclei formation and double strand break (DSB) formation, as compared to undifferentiated hESC upon exposure to genotoxic stress. Nevertheless, H1F cell types displayed comparable sensitivities to genotoxic challenge as HEPM and PBL, both of which are representative of somatic cell types commonly used for genotoxicity screening. Subsequently, transcriptomic and pathways analysis identified differential expression of critical genes involved in cell death and DNA damage response upon exposure to gamma irradiation. The results thus demonstrate that hESC-derived fibroblastic progenies are as sensitive as commonly-used somatic cell types for genotoxicity screening. Moreover, hESCs have additional advantages, such as their genetic normality compared to immortalized cell lines, as well as their amenability to scale-up for producing large, standardized quantities of cells for genotoxicity screening on an industrial scale, something which can never be achieved with primary cell cultures. © 2014 Published by Elsevier B.V.
Authors & Co-Authors
Vinoth, Kumar Jayaseelan
Singapore, Singapore City
Faculty of Dentistry
Singapore, Singapore City
Singapore Health Services
Manikandan, J.
Saudi Arabia, Jeddah
King Abdulaziz University
Australia, Perth
The University of Western Australia
Sethu, Swaminathan
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
India, Vellore
Vellore Institute of Technology
Balakrishnan, Lakshmidevi
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Heng, Alexis
Malaysia, Bandar Sunway
Sunway University
Switzerland, Zurich
Eth Zürich
Lu, Kai
Japan, Kyoto
Institute for Integrated Cell-material Sciences
Hande, Prakash
Singapore, Singapore City
Nus Yong Loo Lin School of Medicine
Singapore, Singapore City
National University of Singapore
Cao, Tong
Singapore, Singapore City
Faculty of Dentistry
Statistics
Citations: 18
Authors: 8
Affiliations: 10
Identifiers
Doi:
10.1016/j.jbiotec.2014.05.009
ISSN:
01681656
e-ISSN:
18734863
Research Areas
Cancer
Genetics And Genomics