Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/26141
Title: ROLE OF HUMAN EMBRYONIC STEM CELLS AND DERIVED PROGENIES IN GENOTOXICITY TESTING
Authors: VINOTH KUMAR S/O JAYASEELAN
Keywords: ES cells, Toxicology testing, Genotoxicity Testing
Issue Date: 20-Jan-2011
Source: VINOTH KUMAR S/O JAYASEELAN (2011-01-20). ROLE OF HUMAN EMBRYONIC STEM CELLS AND DERIVED PROGENIES IN GENOTOXICITY TESTING. ScholarBank@NUS Repository.
Abstract: Established mammalian cell lines are commonly used to analyze the cytotoxic and genotoxic potential of environmental factors, drugs, biomaterials as well as chemical, physical and biological agents in vitro. However, these cells poorly reflect human physiology. Much research is currently being undertaken to find viable alternatives for animal testing. Embryonic stem cells have been validated as a reliable source for in vitro developmental toxicology studies (Klemm et al., 2001; Rohwedel et al., 2001). Furthermore, differentiation of murine embryonic stem cells has enabled cellular screens on large numbers of functional cardiomyocytes (Kehat et al., 2001; Kehat et al., 2002; Mummery et al., 2002) and hepatocytes (Choi et al., 2002; Yamada et al., 2002). However, no such study has been reported on the use of human embryonic stem cells (hESC) and their derived progenies as a cellular model for genotoxicity testing. Hence, much study is required before human embryonic stem cells (hESC) can replace existing animal models for reliable in vitro genotoxicity testing. In this study, the DNA damage response of hESCs and the hESC-derived progenies, derived following spontaneous differentiation of hESCs, were compared to fibroblastic cell lines and peripheral blood lymphocytes. Following this, DNA cross-linking agent, Mitomycin C, as specified by the Organization for Economic Co-operation and Development (OECD) guidelines along with gamma radiation and H2O2 was used to induce damage and the genotoxicity was evaluated. Peptide Nucleic Acid Fluorescence In-Situ Hybridization (FISH) was undertaken to evaluate chromosomal aberrations. Multi-color FISH (mFISH) allowed for further elucidation of the specific type of chromosomal aberrations. This study emphasizes, the use of appropriate cells for genotoxicity testing. Hence, this study highlights the versatility and usefulness of hESCs and their derived progenies for application in genotoxicity testing. This study provides some insight on the response of hESCs and their derived progenies to genotoxic damage and hence potential for the application of hESCs and their derived progenies intoxicology testing of chemical compounds. Therefore, hESCs and their derived progenies may serve as plausible cellular models for in vitro genotoxicity testing.
URI: http://scholarbank.nus.edu.sg/handle/10635/26141
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