TY - JOUR

T1 - Cells from individuals with SOD-1 associated familial amyotrophic lateral sclerosis do not have an increased susceptibility to radiation-induced free radical production or DNA damage.

AU - Mithal, Natasha P.

AU - Radunovic, Aleksandar

AU - Figlewicz, Denise A.

AU - Leigh, P. Nigel

AU - McMillan, Trevor J.

PY - 1999/3/15

Y1 - 1999/3/15

N2 - Oxidative stress may play a role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). Superoxide dismutases (SODs) are enzymes that can influence free radical processes in irradiated cells and there is some evidence that manipulation of SODs can affect survival of cells after radiation treatments. SOD-1 associated FALS mutants may have an altered radiation response due to an enhanced generation of hydroxyl radicals or a compromised 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 induced by ionising radiation by measuring levels of intracellular reactive oxygen species and production of DNA double-strand breaks. Levels of reactive oxygen species, expressed as the slope of the relative fluorescence of a radical-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 DNA double-strand breaks between three groups. The ability of lymphoblastoid cells from FALS patients with SOD-1 gene mutations to scavenge radiation-induced free radicals is not compromised nor is their ability to protect DNA damage induced by ionising radiation.

AB - Oxidative stress may play a role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). Superoxide dismutases (SODs) are enzymes that can influence free radical processes in irradiated cells and there is some evidence that manipulation of SODs can affect survival of cells after radiation treatments. SOD-1 associated FALS mutants may have an altered radiation response due to an enhanced generation of hydroxyl radicals or a compromised 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 induced by ionising radiation by measuring levels of intracellular reactive oxygen species and production of DNA double-strand breaks. Levels of reactive oxygen species, expressed as the slope of the relative fluorescence of a radical-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 DNA double-strand breaks between three groups. The ability of lymphoblastoid cells from FALS patients with SOD-1 gene mutations to scavenge radiation-induced free radicals is not compromised nor is their ability to protect DNA damage induced by ionising radiation.

KW - Amyotrophic lateral sclerosis

KW - SOD-1

KW - Reactive oxygen species

KW - DNA damage

KW - Ionising radiation

U2 - 10.1016/S0022-510X(99)00053-2

DO - 10.1016/S0022-510X(99)00053-2

M3 - Journal article

VL - 164

SP - 89

EP - 92

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1

ER -