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|Author(s):||M Miral Dizdar;|
|Title:||Clemens von Sonntag and the early history of radiation-induced sugar damage in DNA|
|Published:||June 02, 2014|
|Abstract:||This article reviews the early history of radiation-induced sugar damage in DNA in dedication to Prof. Clemens von Sonntag, who recently passed away. It covers the ten years between 1968 and 1978, during which most of the work on the ionizing radiation-induced damage to polyalcohols, carbohydrates and the 2'-deoxyribose moiety in DNA has been performed. Methodologies using gas chromatography-mass spectrometry (GC-MS) were developed to identify and quantify the radiation-induced products that had remained elusive in previous years. The products were identified by GC-MS either directly or after reduction of samples with NaBH4 or NaBD4. Incorporation of deuterium atoms by NaBD4-reduction facilitated the mass spectral identification of aldehyde, keto, carboxyl and deoxy groups in the precursor molecules. Numerous products of a polyalcohol and carbohydrates were identified and quantified. Mechanisms of product formation were proposed. Several radiation-induced products of the 2'-deoxyribose moiety of DNA were identified, indicating that they were released from DNA strand, not bound to it. Alkali labile sites and products still remaining within DNA or bound to DNA as end groups were also elucidated by first reducing irradiated samples with NaBD4 followed by alkali treatment, derivatization and GC-MS analysis. The knowledge of the products led to the first mechanistic understanding of various pathways of hydroxyl radical-induced DNA strand breakage. To this date, some of these mechanisms still remain the most-widely studied mechanisms of DNA damage. Prof. von Sonntag‰s contributions to the understanding of the radiation chemistry of carbohydrates and DNA helped shape this field of science for years to come.|
|Citation:||International Journal of Radiation Biology|
|Pages:||pp. 446 - 458|
|Keywords:||DNA damage, hydroxyl radical, mass spectrometry, mechanisms of product formation, sugar products thaliana, Candida albicans DNA damage, hydroxyl radical, mass spectrometry, mechanisms of product formation, sugar products|
|DOI:||http://dx.doi.org/10.3109/09553002.2014.894652 (Note: May link to a non-U.S. Government webpage)|