Many genotoxins are found in the environment from synthetic to natural, yet very
few have been studied in depth. This means we fail to understand many molecules
that damage DNA, we do not understand the type of damage they cause and the
repair pathways required to correct their lesions. It is surprising so little is
known about the vast majority of genotoxins since they have potential to cause
disease from developmental defects to cancer to degenerative ailments. By
contrast, some of these molecules have commercial and medical potential and some
can be weaponized. Therefore, we need a systematic method to efficiently
generate a genotoxic profile for these agents. A genotoxic profile would include
the type of damage the genotoxin causes, the pathways used to repair the damage
and the resultant mutations if repair fails. Mouse embryonic stem (ES) cells are
well suited for identifying pathways and mutations. Mouse ES cells are
genetically tractable and many DNA repair mutant cells are available. ES cells
have a high mitotic index and form colonies so experiments can be completed
quickly and easily. Furthermore, ES cells have robust DNA repair pathways to
minimize genetic mutations at a particularly vulnerable time in life, early
development when a mutation in a single cell could ultimately contribute to a
large fraction of the individual. After an initial screen, other types of cells
and mouse models can be used to complement the analysis. This review discusses
the merging field of genotoxic screens in mouse ES cells that can be used to
discover and study potential genotoxic activity for chemicals commonly found in
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