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      The application of mass spectrometry in molecular dosimetry: Ethylene oxide as an example

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      Mass Spectrometry Reviews
      Wiley-Blackwell

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          Abstract

          Mass spectrometry plays an increasingly important role in the search for and quantification of novel chemically specific biomarkers. The revolutionary advances in mass spectrometry instrumentation and technology empower scientists to specifically analyze DNA and protein adducts, considered as molecular dosimeters, derived from reactions of a carcinogen or its active metabolites with DNA or protein. Analysis of the adducted DNA bases and proteins can elucidate the chemically reactive species of carcinogens in humans and can serve as risk-associated biomarkers for early prediction of cancer risk. In this article, we review and compare the specificity, sensitivity, resolution, and ease-of-use of mass spectrometry methods developed to analyze ethylene oxide (EO)-induced DNA and protein adducts, particularly N7-(2-hydroxyethyl)guanine (N7-HEG) and N-(2-hydroxyethyl)valine (HEV), in human samples and in animal tissues. GC/ECNCI-MS analysis after HPLC cleanup is the most sensitive method for quantification of N7-HEG, but limited by the tedious sample preparation procedures. Excellent sensitivity and specificity in analysis of N7-HEG can be achieved by LC/MS/MS analysis if the mobile phase, the inlet (split or splitless), and the collision energy are properly optimized. GC/ECNCI-HRMS and GC/ECNCI-MS/MS analysis of HEV achieves the best performance as compared with GC/ECNCI-MS and GC/EI-MS. In conclusion, future improvements in high-throughput capabilities, detection sensitivity, and resolution of mass spectrometry will attract more scientists to identify and/or quantify novel molecular dosimeters or profiles of these biomarkers in toxicological and/or epidemiological studies.

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          Most cited references132

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          Ethylene oxide sterilization of medical devices: a review.

          Ethylene oxide (EO) is a well-known sterilizing agent. However, only recently has its use significantly emerged, based on its range of applications in the field of new medical device development and sterilization. This paper describes the progress in terms of EO sterilization and concludes that it remains a promising field to explore and develop. The EO action mechanism and toxicity are analyzed, and a critical analysis is made on how it is possible to use EO sterilization for medical devices advantageously, with emphasis on cycle design and validation. One huge challenge is related with the development of mathematical models to integrate lethality to allow a continuous increase of process flexibility, without compromising its safety. The scientific community should also focus on other important issues, such as EO diffusion in different substrates, taking into account different environmental conditions both for sterilization and aeration.
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            Protein adducts: quantitative and qualitative aspects of their formation, analysis and applications

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              Evaluation of genetic risks of alkylating agents: Tissue doses in the mouse from air contaminated with ethylene oxide

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                Author and article information

                Journal
                Mass Spectrometry Reviews
                Mass Spectrom. Rev.
                Wiley-Blackwell
                02777037
                2011
                February 2011
                :
                :
                : n/a
                Article
                10.1002/mas.20299
                21328599
                9c124c21-af4d-4bbd-813b-c5d5486646df
                © 2011

                http://doi.wiley.com/10.1002/tdm_license_1.1

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