%0 Journal Article
%T Improvement of genetic stability in lymphocytes from Fanconi anemia patients through the combined effect of ¦Á-lipoic acid and N-acetylcysteine
%A Filipa Ponte
%A Rosa Sousa
%A Ana P Fernandes
%A Cristina Goncalves
%A Jose Barbot
%A Felix Carvalho
%A Beatriz Porto
%J Orphanet Journal of Rare Diseases
%D 2012
%I BioMed Central
%R 10.1186/1750-1172-7-28
%X The objective of the present work is to evaluate the putative protective effect of ¦Á-lipoic acid (¦Á-LA), a mitochondrial protective agent, and N-acetylcysteine (NAC), a direct antioxidant and a known precursor for glutathione synthesis, in spontaneous and DEB-induced chromosome instability (CI) in lymphocyte cultures from FA patients.For that purpose, lymphocyte cultures from 15 FA patients and 24 healthy controls were pre-treated with 20£¿¦ÌM ¦Á-LA, 500£¿¦ÌM NAC and ¦Á-LA plus NAC at the same concentrations, and some of them were exposed to DEB (0.05£¿¦Ìg/ml). A hundred metaphases per treatment were scored to estimate the relative frequency of spontaneous and DEB-induced chromosome breakage.The obtained results revealed that a cocktail of ¦Á-LA and NAC can drastically improve the genetic stability in FA lymphocytes in vitro, decreasing CI by 60% and 80% in cultures from FA patients and FA mosaic/chimera patients, respectively. These results suggest that the studied cocktail can be used as a prophylactic approach to delay progressive clinical symptoms in FA patients caused by CI, which can culminate in the delay of the progressive bone marrow failure and early cancer development.
%K Fanconi Anemia
%K Oxidative stress
%K Antioxidants
%K ¦Á-lipoic acid
%K N-acetylcysteine
%K Chromosome instability
%K Bone marrow failure
%K Cancer susceptibility
%U http://www.ojrd.com/content/7/1/28/abstract