Next Generation Testing Strategies for Assessment of Genotoxicity

Project SummaryIt is well recognized that current batteries of genetic toxicology assays exhibit two critical deficienciesFirstthe throughput capacity of in vitro mammalian cell genotoxicity tests is lowand does not meet current
needsSecondconventional assays provide simplistic binary callsgenotoxic or non genotoxicIn this scheme
there is little or no consideration for potencyand virtually no information is provided about molecular targets
and mechanismsThese deficiencies in hazard characterization prevent genotoxicity data from optimally
contributing to modern risk assessmentswhere this information is essentialWe will address these major
problems with current in vitro mammalian cell genetic toxicity assays by developing methods and associated
commercial assay kits that dramatically enhance throughput capacityand delineate genotoxicantsandaposprimary
molecular targetswhile simultaneously providing information about potencyOnce biomarkers and a family of
multiplexed assays have been developed for these purposesan interlaboratory trial will be performed with
prototype assay kits to assess the transferability of the methods Project NarrativeDNA damage that cannot be faithfully repaired results in gene mutation and or chromosomal
aberrationsand these effects are known to contribute to cancer and other severe diseasesThusthere is an
important need for sensitive assays to evaluate chemicals for genotoxic and other deleterious effectsThe
work proposed herein will address issues that have plagued genotoxicity assessments for the last several
decadeslow throughputlack of potency metricsand little to no information about molecular targetsWe will
address these major problems with current genetic toxicity assays by developing new methods and associated
commercial assay kits