Investigation of a Proposed Mechanism for Genotoxic Effects Induced by 2-Hydroxyalkylating Agents. Kinetics of Intramolecular Transesterification in Dithymidine 2-Hydroxyethyl-and 2-Hydroxypropyl Phosphate

Abstract

Alkylation of DNA gives rise to adducts, not only at the bases, but also at the phosphate groups giving phosphotriesters^1–3. 2-Hydroxy-alkylation of phosphodiester functions in DNA causes considerable strand breakage already in neutral solution⁴. This effect has been suggested to be involved in the higher genotoxicity of 2-hydroxyalkylating agents as compared to, for instance, the corresponding methoxy compounds⁵.