Role of Metallothionein in the Cell Cycle: Protection against the Retardation of Cell Proliferation by Endogenous Reactive Oxygen Species

Abstract

The growth rate of metallothionein (MT)-null (MT-/-) cells was significantly lower than that of wild-type (MT+/+) cells, the cell cycle being arrested at the G₂/M phase in MT-/- cells and endogenous reactive oxygen species (ROS) accumulating with the progress of the cell cycle. Exogenous ROS generated on treatment with H₂O₂ arrested the cell cycle of MT-/- cells at the G₂/M phase more severely than that of MT+/+ cells. These observations suggest that MT maintains the normal cell cycle as an antioxidant against excessive endogenous ROS that are generated synchronously with the cell cycle and disturb the normal cell cycle.