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

Abstract

Massive deguanylation of guanine based-nucleosides induced by halogenated alkanes 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 o C), which were analyzed by HPLC and further confirmed by LC-MS. Among the sixteen different halogenated alkanes, 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 basednucleosides 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 alkanes was also investigated. These results suggest that the toxic effect of certain halogenated alkanes might be from the depurination of nucleosides.

Polyvinyl Pyrrolidone Promotes DNA Cleavage by a ROS-Independent and Depurination Mechanism

“…The presence of fragment ion at m / z 136.1 suggests that P1 is the [M + H] + peak for adenine (Figure c). , The fragmentation spectrum shows major fragment ions from a loss of NH 3 at m / z 119 and one minor fragment (CN 2 H 4 ) at m / z 92. Similarly, the MS/MS spectrum of P2 shows three fragment ions at m / z 152.2, 135.0 and 110.1, and the presence of fragment ion at m / z 152.2 suggests that P2 is the [M + H] + peak for guanine (Figure d). , The release of these nucleobases from dsDNA suggests that the N-glycosidic bond can be broken down by PVP during DNA cleavage. Therefore, we demonstrate that PVPs have an intrinsic activity similar to that of DNA glycosylases, which can hydrolyze bases from nucleosides or DNA.…”

“…Similarly, the MS/MS spectrum of P2 shows three fragment ions at m/z 152.2, 135.0 and 110.1, and the presence of fragment ion at m/z 152.2 suggests that P2 is the [M + H] + peak for guanine (Figure 2d). 46,47 The release of these nucleobases from dsDNA suggests that the Nglycosidic bond can be broken down by PVP during DNA cleavage. Therefore, we demonstrate that PVPs have an intrinsic activity similar to that of DNA glycosylases, which can hydrolyze bases from nucleosides or DNA.…”