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.
Hosford
Mandy E
ME
Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112-0850, USA.
Muller
James G
JG
Burrows
Cynthia J
CJ
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