Validation of Cross-Species Biomarkers of DNA Damage

Project Summary
This project will validate two high throughput human blood based DNA damage assays and develop them
into commercial kitsThe assays monitor types of damage associated with important human diseasesWhereas the PIG A assay reports on gene mutationthe micronucleated reticulocyteMN RETassay is
responsive to chromosomal breaks and or lossesThe biomarkers are applicable to both humans and
laboratory animals and will fulfill two important needsextension of findings in laboratory animal models to
direct studies in humansand performance of well controlled mechanistic laboratory studies to understand
observations first made in humansThe assays utilize immunomagnetic separation prior to flow cytometry to
dramatically enrich the relevant cell populations and thereby enhance assay precision and sensitivityBy
providing simple to use kits with thoroughly documented reproducibility and inter laboratory transferabilityand validating the biomarkers for specific usesresearchers will have available tools with unprecedented
efficiencies for comprehensively studying those factors that contribute to inter individual differences in
human DNA damageApplications include the study of drug treatmentshost and or life style factors that
contribute to inter individual differences in DNA damage and repairexaggerated sensitivities to antineoplastic therapiesand population based epidemiology studies of environmental exposuresincluding
occupational exposuresThe project benefits from a strong multidisciplinary team of internationally
recognized scientists with a proven track record of successfully converting research advances into reliable
commercial assay kits Project Narrative
This project will validate two high throughput human blood based DNA damage assays and develop them
into commercial kitsThe assays represent significant advances in the ability to directly monitor important
types of DNA damage in humansand their cross species nature is ideal for supporting mechanistic
laboratory studies when necessaryValidation work will include but is not limited to assessments of assay
reproducibility within and among laboratoriesvalidation of target cellsand identification of physiological
and lifestyle factors that affect assay resultsThe proposed work also includes the evaluation of several
important use cases for these kitsfor example studying DNA damage resulting from chemotherapiesand
also systemic inflammation