DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 414

(and lower concentrations of anions) near DNA which allow them to scavenge
• OH (thiols and disulfides) and repair DNA radicals (thiols), that is, the interme-
diates responsible for base release.

The effective charge Z of the disulfide derived from WR 1065, WR 33274, is near
+4 and hence accumulates even more strongly near the DNA accounting for very
effective • OH scavenging. In addition, it protects DNA by compaction (Savoye et
al. 1997). It is not homogeneously distributed along the DNA double helix. As a
consequence, there are hot spots of protected and unprotected regions.
Metallothioneins are small ubiquitous oligopeptides containing a high pro-
portion of cysteine residues but no disulfide bonds (Tsunoo et al. 1978; Suzuki
and Maitani 1983). Mammalian metallothioneins (MT-1 and MT-2) are made up
of 61 amino acids, 20 of which are cysteine (Hamer 1986). In vivo, they partici-
pate in the absorption, storage and homeostasis of essential trace metals such as
Zn and Cu (Hamer 1986; Bremner 1987; Kägi and Schäffer 1988; Stillman et al.
1992; Sato and Bremner 1993; Suzuki et al. 1993). In SV79 cells, they are reported
to exert some protective effect (Greenstock et al. 1987; Abel and de Ruiter 1989).
Their reaction with • OH is remarkably high ( k = (1.2-3.5)

10 12 dm 3 mol −1 s −1 ;
Thornalley and Vasak 1985; Fang et al. 1994), but this high rate constant does
not imply a protective role of the metallothioneins in the cellular environment
against • OH (Chap. 3.5).
In all of these reactions, thiyl radicals are formed which are still quite reac-
tive in many aspects (Chap. 7.4). In a cellular environment, they will have to
be inactivated. Originally, O 2 • − was thought to be the radical sink according to
reactions (78) and (79), but more recent kinetic evidence has shown that it may
be the ascorbate radical [reaction (80)] (Wardman 1995, 1998).

×

RS • + RS −

RSSR • −

→ (78)

RSSR • − + O 2 → RSSR + O 2 • − (79)

RS • + Asc − → RS − + Asc • − (80)

12 .11. 3
Bisbenzimidazoles

Bisbenzimidazoles (for a review, see Martin 1998) protect cells against ionizing
radiation (Denison et al. 1992; Lyubimova et al. 2001). Bisbenzimidazoles such
as Hoechst 33258 strongly bind to the minor groove of B DNA (Pjura et al. 1987;
in a dodecamer the Α TTC region is the preferred intercalating site).