Oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by oxyl radicals produced by photolysis of azo compounds.
Oxidative damage to 8-oxo-7,8-dihydroguanine (8-oxoG) bases initiated by photolysis of the water-soluble radical generator 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) has been investigated by laser kinetic spectroscopy. In neutral oxygenated aqueous solutions, 355 nm photolysis of AAPH initiates efficient one-electron oxidation of the 8-oxodG nucleosides directly monitored by the appearance of the 8-oxodG(*+)/8-oxodG(-H)* radicals at 325 nm. The reaction kinetics consist of a mechanism that includes the transformation of the 2-amidinoprop-2-peroxyl radicals (ROO*) derived from photolysis of AAPH to more reactive 2-amidinoprop-2-oxyl radicals (RO*), which directly react with the 8-oxoG bases. The major pathways for the formation of end products of 8-oxoG oxidation include the combination of the 8-oxodG(*+)/8-oxodG(-H)* radicals with superoxide (O(2)(*-)) and ROO* radicals in approximately 1:1 ratios, as demonstrated by experiments with Cu,Zn superoxide dismutase, to form dehydroguanidinohydantoin (Gh(ox)) derivatives. This mechanism was confirmed by analysis of the end products produced by the oxidation of two substrates: (1) the 8-oxoG derivative 2',3',5'-tri-O-acetyl-7,8-dihydroguanosine (tri-O-Ac-8-oxoG) and (2) the 5'-d(CCATC[8-oxoG]CTACC) sequence. The major products isolated by HPLC and identified by mass spectrometry methods were the tri-O-Ac-Gh(ox) and 5'-d(CCATC[Gh(ox)]CTACC products.
Shao
Jie
J
Chemistry Department, New York University, New York, New York 10003-5180, USA.
Geacintov
Nicholas E
NE
Shafirovich
Vladimir
V
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000578:Amidines / Q000737:chemistry*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D007834:Lasers; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry* / Q000633:toxicity; D010782:Photolysis
D000578:Amidines; D010545:Peroxides; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
Free Radic Res. 2004 Apr;38(4):375-84
15190934
Biochemistry. 2000 Apr 11;39(14):4129-35
10747804
Chem Phys Lipids. 2004 Apr;129(1):43-52
14998726
Pharm Res. 2008 Sep;25(9):2097-116
18626751
Chem Res Toxicol. 1995 Apr-May;8(3):379-88
7578924
Curr Cancer Drug Targets. 2006 Nov;6(7):613-22
17100567
Chem Res Toxicol. 2000 May;13(5):390-6
10813656
FEBS Lett. 1990 May 21;264(2):165-7
2358063
Carcinogenesis. 2000 Mar;21(3):361-70
10688856
Curr Med Chem. 2003 Dec;10(24):2631-42
14529453
Anal Biochem. 2009 Mar 15;386(2):167-71
19150323
J Phys Chem B. 2010 May 20;114(19):6685-92
20415485
Chem Res Toxicol. 2006 Apr;19(4):491-505
16608160
Mutat Res. 1994 Jan;304(1):33-105
7506357
Redox Rep. 2008;13(5):225-36
18796242
Chem Res Toxicol. 2003 Sep;16(9):1118-23
12971799
Cell Biol Toxicol. 2009 Dec;25(6):635-44
19152116
J Biol Chem. 2005 Feb 25;280(8):6293-300
15590679
Radiat Res. 1996 May;145(5):532-41
8619018
Free Radic Res. 2007 Jan;41(1):73-81
17164180
Eur Biophys J. 2007 Apr;36(4-5):499-515
17380326
Biochemistry. 2002 Jan 22;41(3):914-21
11790114
Free Radic Biol Med. 2009 Oct 1;47(7):983-91
19596065
Free Radic Res. 2003 Sep;37(9):983-91
14670006
Trends Genet. 1993 Jul;9(7):246-9
8379000
Biochemistry. 2003 Aug 12;42(31):9257-62
12899611
J Biol Chem. 1997 Aug 8;272(32):19633-6
9289489
Biochim Biophys Acta. 2006 Nov;1761(11):1335-43
17052951
Chem Res Toxicol. 2008 Feb;21(2):358-73
18159932
Annu Rev Biochem. 1995;64:97-112
7574505
Org Lett. 2000 Mar 9;2(5):613-6
10814391
Toxicology. 2002 Dec 27;181-182:219-22
12505314