DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 417

attributed to the fact that mitochondrial DNA is deficient in histones that pro-
vide protection in nuclear DNA (Eaton and Qian 2002).
DNA compaction decreases the surface area per molecule exposed to bulk
• OH by 14%. Based on the cylindrical model (Mark et al. 1989), it has been calcu-
lated that competitive scavenging leads to a protection factor of 2, while a factor
of 50 appears as a consequence of compaction (Newton et al. 1996). There is also
a

20% contribution by the direct effect of ionizing radiation on DNA in this
special system.
Intercalation of ethidium bromide into a supercoiled plasmid increases its
target volume at low ethidium bromide concentrations. As a consequence, low
ethidium bromide concentrations sensitize plasmid DNA despite some • OH-
scavenging by the drug (Begusova et al. 2000a). In linear DNA 80 bp fragments,
however, the volume expansion is overcompensated by • OH-scavenging of the
drug, and only protection is observed.
Since in this section compaction of DNA by spermidine has been discussed,
it may be worth mentioning that compaction by spermidine has also an effect
on the photochemistry of DNA. While in non-compacted DNA besides the cis -
syn pyrimidine dimer which requires B-form DNA the formation of some trans -
syn pyrimidine dimer is always observed, but when the DNA is compacted with
spermidine, the formation of the latter is practically fully suppressed (Douki et
al. 2004).

∼

12 .11. 5
Chromatin

When chromatin is -irradiated as an expanded gel, 6 eV are required to induce

an ALS (+ frank SSB) (Mee et al. 1978). This value has to be compared with 80 eV
per ALS (+ frank SSB) in the whole cell. Obviously, in the expanded chromatin
gel the indirect effect of radiation is much more pronounced than in the cel-
lular environment. With DSBs as the measured endpoint, deproteinized DNA
in agarose plugs (i) was compared with DNA organized in the basic nucleosome
repeat (ii) condensation of the chromatin fiber into higher order structure (iii),
and DNA in CHO cells (iv), an increasing protection observed (protection factor
(i)→(ii)

γ

(iv) = 4.5; Warters and Lyons 1992). Thus,
a protection factor near 70 is observed on going from DNA in a gel to the well
protected and condensed DNA in the nucleus. As a consequence, cellular DNA
base damage induced upon whole body

→ (i)→(ii) = 2; (i)→(ii) → (iii) = 8.3; (iii) →

γ -irradiation of mice are only detectable

at high doses (Mori et al. 1993).