Cantoni O, Sestili P, Brandi G, Cattabeni F
Istituto di Farmacologia e Farmacognosia, Università di Urbino, Italy.
FEBS Lett. 1994 Oct 10;353(1):75-8. doi: 10.1016/0014-5793(94)01010-2.
Micromolar concentrations of L-histidine increase the cytotoxicity of hydrogen peroxide in a number of cell lines including CHO (hamster), EAHY, McCoy's, U937 and CCRF-CEM (human), Vero (monkey) and SC-1 (mouse). Importantly, these cell lines displayed different degrees of sensitivity to H2O2 alone and the extent of enhancement elicited by the amino acid was more pronounced in resistant cell lines. The increased cytotoxicity was invariably associated with the formation of DNA DSBs and a remarkable correlation was found by plotting the level of DNA DSBs against the cytotoxic response. These results strongly support the hypothesis that the mechanism whereby L-histidine increases the toxicity elicited by H2O2 involves the formation of DNA DSBs and are consistent with the possibility that the amino acid might participate in the regulation of the physio-pathological response to oxidative stress in mammals.
微摩尔浓度的L-组氨酸会增加过氧化氢对多种细胞系的细胞毒性，这些细胞系包括CHO（仓鼠）、EAHY、 McCoy's、U937和CCRF-CEM（人）、Vero（猴）以及SC-1（小鼠）。重要的是，这些细胞系对单独的过氧化氢表现出不同程度的敏感性，并且氨基酸引发的增强程度在抗性细胞系中更为明显。细胞毒性的增加总是与DNA双链断裂的形成相关，通过绘制DNA双链断裂水平与细胞毒性反应的关系图发现了显著的相关性。这些结果有力地支持了以下假设，即L-组氨酸增加过氧化氢引发的毒性的机制涉及DNA双链断裂的形成，并且与该氨基酸可能参与调节哺乳动物对氧化应激的生理病理反应的可能性一致。
