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Project description:
The project was designed to test the hypothesis that many compounds
with a different primary mode of action would trigger developmental toxicity by
a common mechanism: a change of how the genetic information of a cell is stored
and accessed. This is described in scientific terms as 'epigenetic change'. The
project uses differentiating pluripotent human stem cells as model system to
examine such epigenetic changes. Knowledge of such changes could be used to
define new universal endpoints for in vitro toxicity testing, and thereby help
to replace animal experiments in the field of reproductive toxicity testing.
Outcome (preliminary; until IV/2013):
Balmer NV, Weng M, Zimmer
B, Ivanova VN, Chambers SM, Nikolaeva E, Jagtap S, Sachinidis A, Hescheler J,
Waldmann T, Leist M (2012).
Epigenetic changes and disturbed neural development in a human embryonic stem
cell-based model relating to the fetal valproate syndrome. Hum Mol Genet 21,
4104-4114
Leist M, Lidbury BA, Yang C, Hayden PJ,
Kelm JM, Ringeissen S, Detroyer A, Meunier JR, Rathman JF, Jackson GR, Stolper
G, Hasiwa N (2012) Novel technologies and an overall strategy to allow hazard
assessment and risk prediction of chemicals, cosmetics and drugs with
animal-free methods. ALTEX 29, 373-388
Leist M, Hasiwa N, Daneshian M (2013)
Summary and validation of new animal-free toxicity tests. ALTEX Proceedings 2,
27-37
Weng M,
Zimmer B, Pöltl D, Brög M, Wüllner U, Waldmann T, Leist M (2012). Extensive transcriptional
regulation of chromatin modifiers during human neurodevelopment. PlosOne, 7,
e36708
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