Improvement of genetic stability in lymphocytes from Fanconi anemia patients through the combined effect of α-lipoic acid and N-acetylcysteine

The objective of the present work is to evaluate the putative protective effect of α-lipoic acid (α-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？μM α-LA, 500？μM NAC and α-LA plus NAC at the same concentrations, and some of them were exposed to DEB (0.05？μg/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 α-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.