Chemistry Reference
In-Depth Information
Table 12.7.
Yields of damaged bases (unit: (10
9
bases)
−1
Gy
−1
) formed in monocyte cells
upon
γ
and carbon ion irradiation. (Pouget et al. 2002)
Product
γ
Carbon ion
Tg
97
62
8-oxo-A
3
3
FAPY-A
5
1
8-oxo-G
20
10
FAPY- G
39
22
5HmU
29
12
5ForU
22
11
5-OHdUrd
<0.2
<0.2
12 . 3. 2
Products Derived from the Thymine Moiety
The products derived from T that have been detected in free-radical damaged
DNA are depicted in Fig.12.7.
Tg, 5OH5,6H
2
T, 5, 6H
2
T, 5HmU and 5OH5MeHyd are readily detected by GC/
MS after excision from the damaged DNA and trimethylsilylation (Chap. 13.2).
For the Tg lesion, an ultrasensitive assay is also available that even allows its
detection in cells at a dose as low as 0.25 Gy and to follow its repair (Le et al.
1998).
In model systems, there is always some ForUra besides HMUra, and there
is no reason, why it should not be formed in DNA as well. In model systems
including ODNs, the Fo lesion, also originating from C (see below), is of major
importance. It must also be formed in DNA but cannot be determined by the
GC/MS technique. Under certain conditions, a treatment with repair enzymes
may form a SSB that can be taken as an indication of its presence. Yet, P1 nucle-
ase, for example, cleaves well that lesion in d(GpFo) but not in d(FopG), d(FopA),
d(FopT), d(FopC) (Falcone, Box, 1997). The tandem lesion d(Fop8-oxoG) is also
not hydrolyzed under these conditions.
The attack of
•
OH at the methyl group of T was first followed by the release
of
3
H
2
O from DNA
3
H-labeled at this position (Swinehart and Cerutti 1975).
With
-irradiated in aqueous solution and also within the phage
an in situ protection factor of 9.4 was noticed, and for
E. coli
the corresponding
value was 790. Interestingly, for the formation of the Tg lesion, the protection
factors were noticeably lower, 1.3 and 140, respectively. In the phage, 200 of the
latter lesions are formed at a dose equivalent to 37% survival as indicated by
Φ
X174 DNA
γ
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