Methylperoxyl radicals as intermediates in the damage to DNA irradiated in aqueous dimethyl sulfoxide with gamma rays.
Using agarose gel electrophoresis, we have measured the yields of DNA single-strand breaks (SSBs) for plasmid DNA gamma-irradiated in aerobic aqueous solution. Incubation after irradiation with the base damage repair endonucleases formamidopyrimidine-DNA N-glycosylase (FPG) or endonuclease III (endo III) results in an increase in the yield of SSBs. In the absence of dimethyl sulfoxide (DMSO) during irradiation, this increase is consistent with the yields of known substrates for FPG and endo III as determined by gas chromatography/mass spectrometry. After irradiation in the presence of 1 mol dm-3 DMSO, the increase in the yield of SSBs after enzyme incubation was further enhanced by a factor of about 5 to 7. The magnitude of this effect, the inability of acrylamide or oxygen to suppress it, and its attenuation by N,N,N',N'-tetramethylphenylenediamine (TMPD) or glycerol all suggest that the methylperoxyl radical (derived from DMSO) is involved as an intermediate. Reactions of the methylperoxyl radical (or some other species derived from it) do not result in strand break damage, but are responsible for DNA base damages which are recognized by FPG and endo III.
Milligan
J R
JR
Department of Radiology, University of California at San Diego, La Jolla 92093-0610, USA.
Ng
J Y
JY
Wu
C C
CC
Aguilera
J A
JA
Ward
J F
JF
Kow
Y W
YW
Wallace
S S
SS
Cunningham
R P
RP
D002021:Buffers; D004247:DNA / Q000737:chemistry / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D043382:DNA-Formamidopyrimidine Glycosylase; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004121:Dimethyl Sulfoxide; D004706:Endodeoxyribonucleases / Q000378:metabolism; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D066298:In Vitro Techniques; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D011854:Radiochemistry; D017382:Reactive Oxygen Species; D012996:Solutions; D014867:Water
D002021:Buffers; D004277:DNA, Single-Stranded; D005609:Free Radicals; D017382:Reactive Oxygen Species; D012996:Solutions; D014867:Water; D004247:DNA; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D004121:Dimethyl Sulfoxide