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