DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 416

Fig. 12.15. Effects of polyamines on the • OH-induced strand-breakage of SV40 DNA (putrescine:
open triangles , spermine: filled diamonds ) and SV40 minichromosomes (spermine: open squares )
according to Newton et al. (1996, with permission)

as spermine (+4) and spermidine (+3), but not the smaller putrescine (+2) (for
binding constants see Braunlin et al. 1982) produce condensation of DNA and
chromatin (e.g., Newton et al. 1996).

This polyamine-induced compaction and aggregation of DNA (PICA effect; Gos-
ule and Schellman 1976) leads to a protection of DNA against • OH-attack much
beyond that expected on account of the • OH-scavenging capacity of the poly-
amines ( k ( • OH + putrescine) = 7 10 9 dm 3 mol −1 s −1 , k ( • OH + spermine) = 1.2

×

10 9 dm 3 mol −1 s −1 ; Newton et al. 1996; Douki et al. 2000). Putrescine with only
two positive charges cannot compact DNA and thus does not provide radiation
protection beyond its • OH scavenging capacity (Spotheim-Maurizot et al. 1995a;
Newton et al. 1996; Fig. 12.15).
Similarly, experiments with SV40 DNA and SV40 minichromosomes (SV40
DNA covered with histones; Oudet et al. 1989) have also shown a dramatic pro-
tective effect upon neutralization of the negatively-charged DNA by the proton-
ated polyamines, and DNA compaction (Fig. 12.15). In the SV40 minichromo-
somes, this occurs already at a lower spermine concentration, because the DNA
surface charge is already partially compensated by the histones. In SV40 DNA,
the protective effect on going from 1

×

10 −3 mol dm −3
spermidine is as much as 145 (Fig. 12.15). The higher steady-state level of dam-
aged bases in mitochondrial DNA as compared to nuclear DNA has, in part, been

10 −3 mol dm −3 to 4

× − 9 ×