Zn2+-dependence of the synergistic increase in rat thymocyte cell lethality caused by simultaneous application of 4,5-dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) and H2O2

- 4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) is an antifouling agent.
- DCOIT and H2O2 induced a synergistic cytotoxicity in rat thymocytes.
- DCOIT increased intracellular Zn2+ concentration.
- The synergistic action was suppressed by chelating intracellular Zn2+.
- DCOIT may exert Zn2+-dependent cytotoxicity under oxidative stress.

4,5-Dichloro-2-octyl-4-isothiazolin-3-one (DCOIT) is an antifouling agent that is an alternative to organotins such as tributyltin (TBT). Because DCOIT decreases catalase activity, it may increase the susceptibility of cells to oxidative stress. We examined the effects of DCOIT on rat thymocytes suffering from oxidative stress induced by H2O2. The simultaneous application of DCOIT and H2O2 induced a synergistic increase in cell lethality that was completely suppressed by chelating intracellular Zn2+. Intracellular Zn2+ concentration was increased by DCOIT at concentrations ranging from 0.1 μM to 3 μM. Although the increase in cell lethality produced by DCOIT alone was less than that produced by TBT alone, a synergistic increase was not induced by the combination of TBT and H2O2. Therefore, these results suggest that DCOIT increases vulnerability to oxidative stress and is more cytotoxic than TBT when oxidative stress is induced by H2O2.