Deguanylation of Guanine Based-Nucleosides and Calf Thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Massive deguanylation of guanine based-nucleosides induced by halogenated alkalies at the physiological condition have been observed. For the study of deguanylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with guanine based-nucleosides (ddG, dG and guanosine) for 48 h at the physiological condition (pH 7.4,37 degrees C), which were analyzed by H PLC and further confirmed by LC-MS. Among the sixteen different halogenated alkalies, we observed massive deguanylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deguanylation rate was highest in 2-bromo-2-methylpropane followed by 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. In addition, time and dose response relationship of deguanylation in guanine based-nucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. Deguanylation of calf thymus DNA induced by halogenated alkalies was also investigated. These results suggest that the toxic effect of certain halogenated alkalies might be From the depurination of nucleosides.