ANALYSIS OF THE MALONDIALDEHYDE-2'-DEOXYGUANOSINE ADDUCT IN RAT-LIVERDNA BY GAS-CHROMATOGRAPHY ELECTRON-CAPTURE NEGATIVE CHEMICAL-IONIZATION MASS-SPECTROMETRY
Ak. Chandhary et al., ANALYSIS OF THE MALONDIALDEHYDE-2'-DEOXYGUANOSINE ADDUCT IN RAT-LIVERDNA BY GAS-CHROMATOGRAPHY ELECTRON-CAPTURE NEGATIVE CHEMICAL-IONIZATION MASS-SPECTROMETRY, Biological mass spectrometry, 23(8), 1994, pp. 457-464
Malondialdehyde (MDA), a product of lipid peroxidation, causes mutatio
ns in bacterial and mammalian cells and cancer in rats. MDA reacts wit
h deoxynucleosides in vitro and the monomeric adduct of MDA with deoxy
guanosine (M(1)G-dR) is the major adduct formed. We have developed a s
ensitive analytical method to characterize and quantify M(1)G-dR from
biological matrices using gas chromatogrphy/electron capture negative
chemical ionization mass spectrometry (GC/ECNCI MS). Reduction of M(1)
G-dR with sodium borohydride produced a dihydro derivative (H-2-M(1)G-
dR). This more stable analog had improved high-performance liquid chro
matographic characteristics which facilitated its isolation from biolo
gical fluids. H-2-M(1)G-dR was converted to a monopentafluorobenzyl de
rivative with simultaneous depurination; it was then converted to the
corresponding t-butyldimethylsilyl derivative and analyzed by GC/ECNCI
MS. (H-2(2))H-2-M(1)G was used as internal standard. Quantitative ana
lysis was carried out using selected ion monitoring of m/z 302 and m/z
304 where the limit of detection was 10 pg (30 fmol) injected on-colu
mn. The level of M(1)G-dR in normal rat liver was 5.2 +/- 0.2 modified
bases per 10(7) bases (n = 6 rats).