L-HISTIDINE-MEDIATED ENHANCEMENT OF HYDROGEN PEROXIDE-INDUCED CYTOTOXICITY - RELATIONSHIPS BETWEEN DNA SINGLE/DOUBLE STRAND BREAKAGE AND CELL-KILLING

Results presented in this study demonstrate an association between the L-Histidine-mediated enhancement of H2O2-induced cytotoxicity and the formation of DNA double strand breakage (DSB), whereas no relationship exists between the increased cytotoxic response and DNA single strand breakage (SSB). Indeed, the higher lethality and the production of DNA DSB occurred in oxidatively-injured cells regardless of whether the exposure to L-Histidine was performed before or during challenge with the oxidant. In fact, the increased level of DNA SSB detected in cells simultaneously exposed to the oxidant and the amino acid was not observed in cells pre-treated with L-Histidine and then challenged with hydrogen peroxide. Further experiments have demonstrated an association between the kinetics of DNA DSB formation and the enhancement of the cytotoxic response. In conclusion, intracellular L-Histidine seems to mediate the formation of DNA DSB and the increased growth-inhibitory response elicited by the oxidant. In addition, these results suggest that the enhancement of DNA SSB is produced by the extracellular/plasma membrane fraction of the amino acid and not causally related to the L-Histidine-mediated increase of the growth-inhibitory response to H2O2-treated cells. © 1994.