The biotransformation and oxidative stress may contribute to 1,2:3,4-
diepoxybutane (DEB)-induced toxicity to human lymphocytes of
Fanconi Anemia (FA) patients. Thus, the identification of putative inhibitors of bioactivation, as well as the determination of the protective role of
oxidant defenses, on DEB-induced toxicity, can help to understand what is failing in FA cells. In the present work we studied the contribution of several biochemical pathways for DEB-induced acute toxicity in human lymphocyte
suspensions, by using inhibitors of
epoxide hydrolases, inhibitors of protective
enzymes as
glutathione S-transferase and
catalase, the depletion of
glutathione (GSH), and the inhibition of
protein synthesis; and a variety of putative protective compounds, including
antioxidants, and mitochondrial
protective agents. The present study reports two novel findings: (i) it was clearly evidenced, for the first time, that the acute exposure of freshly isolated human lymphocytes to DEB results in severe GSH depletion and loss of
ATP, followed by cell death; (ii)
acetyl-l-carnitine elicits a significant protective effect on DEB induced toxicity, which was potentiated by α-
lipoic acid. Collectively, these findings contribute to increase our knowledge of DEB-induce toxicity and will be very useful when applied in studies with lymphocytes from FA patients, in order to find out a
protective agent against spontaneous and DEB-induced
chromosome instability.