DNA and Double-Stranded Oligonucleotides - Free-Radical-Induced DNA Damage and Its Repair - page 423

Table 12 . 22 . Non-protein sulfhydryl (NPSH) and glutathione (GSH) content (µmol/mg
protein) of normal (GSH +/+ ) and GSH-deficient (GSH −/− ) mammalian cells and the radiation
response of these cells. (Revesz 1985)

GSH +/+ GSH −/−

NPSH 12.9 6.0

GSH 11.6 0.7

OER of SSB 3.0 1.2

OER of survival 2.9 1.5

OER of survival, Cya 1 × 10 − 3 mol dm − 3 3.2 1.8

OER of survival, Cya 20 × 10 − 3 mol dm − 3

4.1 2.3

MER of SSB 1.9 1.0

MER of survival 2.3 1.5

OER, Oxygen enhancement ratio; MER misonidazole enhancement ration; Cya, cysteamine

of WR 1065 relevant for • OH-scavenging and repair were determined by pulse
radiolysis (Ward and Mora-Arellano 1984). The use of these drugs seems not
to be without hazard, since with WR 1065 selective denaturation of nonhistone
nuclear proteins is observed (Botth et al. 2000). It also retards the rate of rejoin-
ing SSBs (Murray et al. 1988a, b).
The radiation response of cells from a GSH-synthetase-deficient patient and
its clinically healthy brother are compared in Table 12.22. There, it is seen that
the GSH deficiency results in a lower OER both of survival and SSB formation.
This is largely due to a reduction of GSH, since the other non-protein sulf hy-
dryls (NPSH) are not markedly suppressed in this mutant. The efficiency of GSH
has been attributed to its particular spatial distribution, since exogenous thiols
(here: cysteamine) cannot substitute for this. Other sensitizers such as misoni-
dazole (see below) behave similar as O 2 with respect to SSB formation in these
two cell lines.
As one might expect from the above, there is a correlation between the OER
and the NPSH content in mammalian cells (Cullen et al. 1980). The NPSH level
may be reduced by the addition of several drugs such as BSO, DIAMIDE or NEM
(for reviews see Bridges 1969; Biaglow et al. 1983; Shenoy and Singh 1985).