Low levels of hydrogen peroxide and L-histidine induce DNA double-strand breakage and apoptosis

The results presented in this study demonstrate that L-histidine triggers a lethal response in U937 cells exposed to nontoxic, albeit growth-inhibitory, levels of H2O2. Treatment for 1 h with the cocktail H2O2/L-histidine promotes the formation of a low level of DNA double-strand breaks that are rapidly rejoined, and this process is followed by secondary DNA fragmentation at about 7 h of post-treatment incubation, at which time cells are still viable. The appearance of oligonucleosomal DNA fragments associated with the detection of morphological changes typical of apoptosis strongly suggests that a portion of the cells was undergoing an apoptotic process. The relative level of cells with fragmented chromatin never exceeded 15-20% throughout the 20 h post-treatment incubation. Treatment with high concentrations of H2O2 in the presence of L-histidine was found to trigger necrotic cell death. The results presented in this paper provide further experimental evidence in support of the notion that DNA double-strand breaks mediate the lethal effects of the cocktail H2O2/L-histidine and suggest that this type of DNA lesion can promote both apoptotic and necrotic cell death, depending on the concentration of the oxidant.