Simultaneous protective and damaging effects of cysteamine on intracellular DNA of leukocytes.
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.
Kanabus-Kaminska
J M
JM
Department of Experimental Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
Feeley
M
M
Birnboim
H C
HC
D003543:Cysteamine / Q000494:pharmacology*; D004247:DNA / Q000097:blood / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism
D003543:Cysteamine; D004247:DNA; D006861:Hydrogen Peroxide