L-GLUTAMINE PREVENTS THE L-HISTIDINE-MEDIATED ENHANCEMENT OF HYDROGEN PEROXIDE-INDUCED CYTOTOXICITY

Results presented in this study demonstrate that L-glutamine, a competitive inhibitor of L-histidine uptake, inhibits in a concentration-dependent fashion the L-histidine-mediated enhancement of H2O2-induced cytotoxicity. L-Glutamine also prevents the induction of DNA double strand breaks (DSB) but does not affect the enhancing effect Of L-histidine on DNA single strand break induction by H2O2. Taken together, these data demonstrate that L-histidine, in order to allow the formation of DNA double strand breakage and increase the toxicity elicited by the oxidant, has to enter the cell. In addition, these results indicate that the enhancement of DNA single strand breakage is a consequence of the action of the amino acid at the extracellular level and/or outer surface of the plasma membrane and does not appear related to the mechanism whereby L-histidine increases the cytotoxic response to H2O2. The latter mechanism very likely involves the formation of DNA DSB.