Project 4: Measurement and Engineering Solutions to Detect and Prevent N-Nitrosamine Exposure

项目摘要/摘要-项目4

PROJECT SUMMARY/ABSTRACT – PROJECT 4 N-nitroso (-N-N=O) compounds include some of the most powerful chemical mutagens known and encompass a family of chemicals with hundreds of different structures. However, only a handful of N-nitrosamines are routinely measured via EPA Standard Methods, and these methods are not effective at the low levels anticipated to cause health impacts. To overcome this challenge and reduce human exposure, Project 4 seeks to measure and destroy a suite of N-nitrosamines at the point of use in homes, where they are needed most to protect public health and the environment. First, Specific Aim 1 is to develop methods to detect a suite of established and novel N-nitrosamines using multi-dimensional gas chromatography paired with both mass spectrometry (for identification) and flame ionization detection (for quantification with authentic standards or via an effective carbon number concept when authentic standards can be neither synthesized nor purchased). This technique enables estimation of nearly a dozen critical environmental parameters, such that novel molecules detected in complex mixtures will have at-the-ready physicochemical metrics to feed environmental fate models and predict exposure. Water samples will be collected in collaboration with the Community Engagement Core using traditional collection methods as well as novel Recognition-Solid Phase Extraction (R-SPEs) materials that concentrate N- nitrosamines (to be developed in Project 3), and fractions of extracts will be provided to Project 2 for mutagenicity assessment. Knowledge about the levels of NDMA will inform Project 1 so that environmentally relevant levels can be studied for their biological impacts using novel genetically engineered mice that are sensitized to NDMA. In addition, the Data Management and Analysis Core will integrate data for “what” and “how much” with data on biological impact to inform risk. Armed with knowledge of environmental levels of N-nitrosamines, Specific Aim 2 is to develop novel in-home water filtration technologies based on electrochemical processes and molecular recognition with enzymatic destruction. The latter relies on genetically engineered microbes that act as non-living scaffolds for enzymes; as such, it overcomes many classical challenges faced by bioreactors and opens up vast possibilities to leverage advances in biotechnology for long-awaited revolutions in water treatment. Specific Aim 3 will test the degradation products to ensure that they are no longer genotoxic by collaborating with Project 1 to use “Chem-Sense” cells that act as animate detectors of DNA damage. Trainees will drive the research and will be supported by the Research Experience and Training Coordination Core to ensure optimal professional development. In addition, Project 4 will benefit from activities organized by the Administrative Core that ensure close collaborations with other Projects and with the Cores, as well as opportunities for research translation to stakeholders, including people living near the Olin Chemical Superfund Site and the Passamaquoddy Tribe. Via a Systems Approach of interactions and interdependencies, Project 4 will contribute to the protection of human health from hazardous substances.