Chemistry Reference
In-Depth Information
-irradiated DNA are given in Tables 12.5-12.7. FAPY-G
has always been observed, but 8-oxo-G yields were extremely low, when
The product yields in
γ
-ir-
radiations were carried out under N
2
. This may serve as a caveat for the com-
mon practice to use 8-oxo-G as a kind of 'marker' for free-radical DNA damage
(for assays see Chap. 13.2). Besides the other products reported in Table 12.5,
8 cG lesions per 10
6
bases are formed per Gy in
γ
-irradiated N
2
O-saturated DNA
(50 µg ml
−1
) solution (Dizdaroglu et al. 2001a; corresponding to 1.6
γ
10
−9
mol
×
J
−1
), and this lesion has also been observed in
-irradiated cultured human cells
(Dizdaroglu 1986; for its elimination by nucleotide excision repair see Kuraoka
et al. 2000).
G has the lowest redox potential among the nucleobases (Chap. 10.2 and
Sect. 12.10). Inorganic radicals that have a sufficiently high oxidation potential
(Chap. 5) may be used to oxidize specifically G. One of them is SeO
3
•
−
. Its rate
constant with DNA has been determined at 3
γ
10
7
dm
3
mol
−1
s
−1
(Martin and
Anderson 1998), about one order of magnitude slower than the rate constant of
•
OH (
k
= 4.5
×
10
8
dm
3
mol
−1
s
−1
; Udovicic et al. 1994). Upon one-electron oxi-
dation G
•
+
is formed which subsequently deprotonates yielding G
•
. Due to hole
transfer w ithin DNA, G
•
is possibly the most abundant DNA radical (Sect. 12.10).
It does not react with O
2
and thus can persist for a long time in oxygenated so-
lutions (Chap. 10.2). It may be reduced (repair of DNA damage) by compounds
having a lower reduction potential (Milligan et al. 2001b), and for the reduction
by tryptophan a rate constant of 10
7
dm
3
mol
−1
s
−1
has been given. The rate of
repair by substituted phenols varies with their reduction potentials, and, for ex-
ample, 4-cyanolphenol (E
7
= + 1.17 V) reacts with 7.3
×
10
5
dm
3
mol
−1
s
−1
while
×
4-aminophenol (E
7
= +0.41 V) reacts with 4.7
10
9
dm
3
mol
−1
s
−1
(Milligan et al.
2004). The rate constant of the DNA-binding drug
Hoechst 3358
with G
•
is 1.7
×
×
10
9
dm
3
mol
−1
s
−1
(Table 12.17; for its protection of DNA, see Sect. 12.11).
As with other reducing agents, G
•
reacts with O
2
•
−
(Chap. 10.2) which is the
most abundant freely diffusing peroxyl radical. Upon two-photon excitation of a
2-aminopurine-containing ss- and dsODN in air-saturated solutions, photoion-
ization leads to the formation of e
aq
−
(and subsequently O
2
•
−
) and the 2-amino-
purine radical cation oxidizes a neighboring G (leading to G
•
plus H
+
; Misiaszek
et al. 2004). G
•
and O
2
•
−
react with one another (ssDNA:
k
= 4.1
10
8
dm
3
mol
−1
×
s
−1
; dsDNA: 2.7
10
8
dm
3
mol
−1
s
−1
). In the majority of these events G is re-
formed, but with an efficiency of 15% Iz and, to a minor extent, 8-oxo-G are
formed. The suggested mechanism is shown in Chapter 10.2.
In the reactions of peroxynitrite, CO
3
•
−
plays a major role (Chap. 2.2). In the
self-complementary ODN d(AACGCGAATTCGCGTT) it reacts (
k
= 1.9
×
10
9
dm
3
mol
−1
s
−1
) exclusively with G (by ET) inducing an alkali-labile lesion (Shafirov-
ich et al. 2004). When NO
•
and O
2
•
−
is generated simultaneously as precursors
of peroxynitrite that forms
•
OH and
•
NO
2
upon its decay and when CO
2
is pres-
ent CO
3
•
−
and
•
NO
2
(Chap. 2.4), formation of 8-oxo-G is observed (Inoue and
Kawanishi 1995) and also upon peroxynitrite addition to DNA (Douki and Cadet
1996). In the latter experiments, the effect of peroxynitrite was compared with
that of ionizing radiation, but although the peroxynitrite concentration applied
was 1000 times the radiolytic
•
OH yield, the 8-oxo-G and Z yields were mark-
edly lower. Only very low 8-oxo-G yields were also detected in another study
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