Kanabus-Kaminska J M, Feeley M, Birnboim H C
Department of Experimental Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
Free Radic Biol Med. 1988;4(3):141-5. doi: 10.1016/0891-5849(88)90021-4.
Incubation of human leukocytes with cysteamine can lead to the induction of DNA strand breaks. The induction of breaks is biphasic with increasing concentration of scavenger. The number of breaks increases in a dose-dependent manner to a maximum and then decreases at higher concentrations. Catalase has been shown to prevent the production of breaks, indicating an involvement of hydrogen peroxide. Cysteamine reacts with oxygen to generate hydrogen peroxide but at higher concentrations it also reacts with hydrogen peroxide. Thus, the biphasic effect of cysteamine on leukocyte DNA may be due to the sum of two separate reaction pathways. (i) Cysteamine reacts with oxygen to generate hydrogen peroxide which leads to DNA strand breakage. (ii) At higher concentrations, it eliminates hydrogen peroxide by reacting with it, thereby protecting the cellular DNA. Other antioxidant scavengers such as WR2721, acetylcysteine and ascorbate can also autooxidize to produce strand breaks. Thiourea and tetramethylurea do not. When tested for their ability to protect cells against DNA damage from added H2O2, the agent which most damaging by itself, cysteamine, was also the most protective.
用半胱胺孵育人白细胞可导致DNA链断裂。随着清除剂浓度的增加，断裂的诱导呈双相性。断裂的数量以剂量依赖的方式增加到最大值，然后在更高浓度时减少。过氧化氢酶已被证明可防止断裂的产生，表明过氧化氢参与其中。半胱胺与氧气反应生成过氧化氢，但在更高浓度下它也与过氧化氢反应。因此，半胱胺对白细胞DNA的双相作用可能是由于两个独立反应途径的总和。（i）半胱胺与氧气反应生成过氧化氢，导致DNA链断裂。（ii）在更高浓度下，它通过与过氧化氢反应消除过氧化氢，从而保护细胞DNA。其他抗氧化剂清除剂如WR2721、乙酰半胱氨酸和抗坏血酸也可自动氧化产生链断裂。硫脲和四甲基脲则不会。当测试它们保护细胞免受添加的H2O2造成的DNA损伤的能力时，自身最具损伤性的试剂半胱胺也是最具保护作用的。
