Deadenylation of Adenine Based-Nucleosides and Calf thymus DNA Induced by Halogenated Alkanes at the Physiological Condition

Massive deadenylation of adenine based-nucleosides induced by halogenated alkanes at the physiological condition have been observed. For the study of deadenylation effects by the different substituents and/or functionality in halogenated alkanes, diverse kinds of halogenated alkanes were incubated with adenine based-nucleosides (ddA, dA and adenosine) for 48 h at the physiological condition (pH 7.4, $37\;{^{\circ}C}$), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, we observed massive deadenylation of nucleosides by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane. The order of deadenylation 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 deadenylation in adenine based-nucleosides induced by 2-bromo-2-methylpropane, 2,3-dibromopropene, 2-bromopropane, bromoethane and 2-iodopropane at the physiological condition were investigated. In addition, deadenylation of calf thymus DNA induced by halogenated alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.