Cells from individuals with SOD-1 associated familial amyotrophic lateral sclerosis do not have an increased susceptibility to radiation-induced freeradical production or DNA damage

Oxidative stress may play a role in the pathogenesis of familial amyotrophi c lateral sclerosis (FALS). Superoxide dismutases (SODs) are enzymes that c an influence free radical processes in irradiated cells and there is some e vidence that manipulation of SODs can affect survival of cells after radiat ion treatments. SOD-1 associated FALS mutants may have an altered radiation response due to an enhanced generation of hydroxyl radicals or a compromis ed ability to neutralize free radicals. We have investigated the ability of the lymphoblastoid cell lines from FALS patients with SOD-1 gene mutations , patients with sporadic ALS and controls to handle oxidative stress induce d by ionising radiation by measuring levels of intracellular reactive oxyge n species and production of DNA double-strand breaks. Levels of reactive ox ygen species, expressed as the slope of the relative fluorescence of a radi cal-reactive fluorochrome, in the cells from familial ALS patients with SOD -1 gene mutations (2.14+/-1.06 Gy(-1)) and patients with sporadic ALS (1.38 +/-0.21 Gy(-1)) were not significantly different from the controls (1.54+/- 0.39 Gy(-1)). No significant difference was observed in the production of D NA double-strand breaks between three groups. The ability of lymphoblastoid cells from FALS patients with SOD-1 gene mutations to scavenge radiation-i nduced free radicals is not compromised nor is their ability to protect DNA damage induced by ionising radiation. (C) 1999 Elsevier Science B.V. All r ights reserved.