Synthesis, characterization and in vtro identification of N7-guanine adduct of 2-bromopropane.

Recently, we have reported that 2-bromopropane might have an immunotoxic potential in rats when exposed for 28 days. In the present studies, the possibility of 2i-deoxyguanosine adduct formation by 2-bromopropane was investigated in vitro to elucidate molecular mechanism of 2-bromopropane-induced immunosuppression. N7-Guanine adduct of 2'-bromopropane (i.e., N7-isopropyl guanine) was chemically synthesized and structurally characterized by analysis of UV, 1H-NMR, '3C-NMR, COSY and fast atom bombardment mass spectrometry to use as a reference material. Incubation of 2'-deoxyguanosine with an excess amount of 2-bromopropane in PBS buffer solution, pH 7.4, at 37 degrees C for 16 h, followed by a thermal hydrolysis, produced a detectable amount of N7-isopropyl guanine by an HPLC and UV analysis. The present results suggest that 2-bromopropane might form a DNA adduct in N7 position of 2'-deoxyguanosine at a physiological condition.