Clemens von Sonntag and the early history of radiation-induced sugar damage in DNA

Abstract

Purpose: This article reviews the early history of ionizing radiation-induced sugar damage in DNA in dedication to Prof. Clemens von Sonntag, who recently passed away. It covers the time between 1968 and 1978, during which most of the work on the ionizing radiation-induced damage to polyalcohols, carbohydrates and the 2ʹ-deoxyribose moiety in DNA was performed. Methodologies using gas chromatography-mass spectrometry (GC-MS) were developed to identify and quantify the radiation-induced products that had previously remained elusive. 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 identification of aldehyde, keto, carboxyl and deoxy groups in the molecules. Numerous products of a polyalcohol and carbohydrates were identified and quantified. Mechanisms of product formation were proposed. Several products of the 2ʹ-deoxyribose moiety in 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 and GC-MS analysis.

Conclusion: The knowledge of the products of the 2ʹ-deoxyribose moiety in DNA 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.

Keywords::

• DNA damage
• free radicals
• radiation chemistry

Declaration of interest

The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.