Spermine participates in oxidative damage of guanosine and 8-oxoguanosine leading to deoxyribosylurea formation.
Oxidation of single- or double-stranded DNA containing a 7,8-dihydro-8-oxoguanosine lesion with the one-electron oxidant Na2IrCl6 in the presence of spermine led to formation of a covalent adduct that was analyzed by gel electrophoresis, HPLC, ESI-MS, and UV-vis. The adduct was labile to heat, exhibiting a t1/2 of 12 h at 37 degrees C, and the ultimate hydrolysis product was characterized as a deoxyribosylurea lesion. Data from model studies with 1,3-diaminopropane vs 1,4-diaminobutane are consistent with initial formation of a C5 spermine adduct from a dehydro-8-oxoguanosine intermediate, followed by rearrangement to a spiroaminal subject to slow hydrolysis at C4 of the purine. Spermine adducts could also be formed from oxidation of the analogous G-containing oligomer from reaction with singlet oxygen, albeit in lower yield. These results are surprising in light of the traditional view that spermine is radioprotective against DNA oxidation.
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, USA.
Mandy E
ME
Hosford
James G
JG
Muller
Cynthia J
CJ
Burrows
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*; D003855:Deoxyribose / Q000031:analogs & derivatives* / Q000378:metabolism; D006151:Guanosine / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D013096:Spermine / Q000737:chemistry / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives* / Q000378:metabolism
D018736:DNA Adducts; D004277:DNA, Single-Stranded; D006151:Guanosine; D013096:Spermine; D003855:Deoxyribose; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014508:Urea; D004247:DNA; D003849:Deoxyguanosine