Abstracts From the 55th Annual Meeting of the Environmental Mutagenesis and Genomics Society, September 7 – 11, 2024 ‐ Palm Springs, CA, USA, An Oasis of DNA Discoveries

Deficiencies in most DNA repair proteins lead to an increase in susceptibility to disease.To learn about the biological impacts of DNA damage, the Engelward laboratory has done work developing in vivo and in vitro approaches for revealing how our genes, our physiology, and our environment impact susceptibility to DNA damage-induced mutations and cancer.In particular, the Engelward lab created genetically engineered mice that make it possible to use fluorescence to detect large scale sequence rearrangements driven by homologous recombination.Using this model, the Engelward lab has investigated not only genetic susceptibility factors, but also susceptibility factors that go beyond our genes, such as inflammation, age, and sex.In addition, the Engelward lab has also developed in vitro tools that can be used to assess genotoxicity and toxicity.As examples, using a mammalian cell array approach, the CometChip detects DNA damage while the MicroColonyChip can be used to assess cell growth.Of particular concern are the many thousands of industrial chemicals for which we have little information on their genotoxic potential.The CometChip has been shown to be useful for assessing the DNA damaging potential of many chemicals.Furthermore, by monitoring damage over time, the CometChip enables assessment of DNA repair in different people, showing that DNA repair capacity in cells from different individuals is highly variable.Taken together, through the development of various approaches for assessing DNA damage, sequence rearrangements, and DNA repair, insights have been gained on risk factors that modulate cancer risk, as well as underlying mechanisms of cancer etiology.