PMID- 18498216
OWN - NLM
STAT- MEDLINE
DCOM- 20080829
LR  - 20131121
IS  - 1547-3287 (Print)
IS  - 1547-3287 (Linking)
VI  - 17
IP  - 3
DP  - 2008 Jun
TI  - Human embryonic stem cells may display higher resistance to genotoxic stress as 
      compared to primary explanted somatic cells.
PG  - 599-607
LID - 10.1089/scd.2007.0088 [doi]
AB  - The use of human embryonic stem (hES) cells in genotoxicity screening can 
      potentially overcome the deficiencies associated with using immortalized cell 
      lines, primary explanted somatic cells, and live animal models. Hence this study 
      sought to compare the responses of hES cells and primary explanted somatic cells 
      (IMR-90 cells, human fetal lung fibroblasts) to genotoxic stress, to evaluate 
      whether hES cells can accurately reflect the normal physiology of human somatic 
      cells. The effects of mitomycin C (MMC) on the chromosomal stability of hESC and 
      IMR-90 was assayed and compared by fluorescence in situ hybridization (FISH) with 
      telomere-specific peptide nucleic acid and multicolor (m) FISH techniques. The 
      results showed that, the percentage of aberrant cells increased from 6% in the 
      untreated control to 57.5% at the higher dose of 0.06 microg/ml MMC (9.6-fold 
      increase) group in the case of IMR-90 cells, whereas hES cells displayed a 
      corresponding increase from 6% to 28% (4.6-fold increase). Telomere FISH 
      ascertained that the main types of damage induced by MMC are chromosomal breaks 
      and the loss of telomeric signals. No fusions were observed in all samples 
      analyzed. This was further confirmed by mFISH, which showed that fusions and 
      translocations were not the type of aberration induced by MMC, with no such 
      aberrations being observed in all samples analyzed. Hence, hES cells of the H1 
      line are apparently more resistant to MMC-induced DNA damage, as compared to the 
      IMR-90 cells. These results highlight possible intrinsic differences in response 
      to damaging agents between hES cells and normal somatic cells.
FAU - Vinoth, Kumar Jayaseelan
AU  - Vinoth KJ
AD  - Stem Cell Program, Faculty of Dentistry, National University of Singapore, 119074 
      Singapore.
FAU - Heng, Boon Chin
AU  - Heng BC
FAU - Poonepalli, Anuradha
AU  - Poonepalli A
FAU - Banerjee, Birendranath
AU  - Banerjee B
FAU - Balakrishnan, Lakshmidevi
AU  - Balakrishnan L
FAU - Lu, Kai
AU  - Lu K
FAU - Hande, M Prakash
AU  - Hande MP
FAU - Cao, Tong
AU  - Cao T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Stem Cells Dev
JT  - Stem cells and development
JID - 101197107
RN  - 0 (Peptide Nucleic Acids)
RN  - 50SG953SK6 (Mitomycin)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chromosome Breakage/drug effects
MH  - *DNA Damage/drug effects
MH  - *Drug Resistance/drug effects
MH  - Embryonic Stem Cells/*metabolism
MH  - Fibroblasts/drug effects/*metabolism
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Metaphase/drug effects
MH  - Mice
MH  - Mitomycin/pharmacology
MH  - Peptide Nucleic Acids/metabolism
MH  - Telomere/metabolism
EDAT- 2008/05/24 09:00
MHDA- 2008/08/30 09:00
CRDT- 2008/05/24 09:00
PHST- 2008/05/24 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/05/24 09:00 [entrez]
AID - 10.1089/scd.2007.0088 [doi]
PST - ppublish
SO  - Stem Cells Dev. 2008 Jun;17(3):599-607. doi: 10.1089/scd.2007.0088.