Low dose exposure to cadmium and its health effects. (3) Toxicity in laboratory animals and cultured cells

We have reviewed studies on cadmium (Cd) toxicity in laboratory animals and cultured cells with special attention to the disruption in cellular signal transduction, involvement in apoptosis of Cd, the cellular transport system for Cd and roles of metallothionein as a protective factor against Cd. Cd affects cellular functions by perturbing signal transductions, such as protein kinase C, mitogen-activated protein kinase and cyclic AMP pathways, but how the disruption of these pathways by Cd leads to the manifestation of toxicity in vivo is largely unknown. Exposure to cadmium at relatively high and low levels causes necrosis and apoptosis, respectively, which suggests that the mode of cell death by cadmium is dependent upon its exposure level. On the other hand, utilization of Ca2+ channels, DMT1 (divalent metal transporter 1) and a novel transport system having high-affinity for Mn2+ and Cd2+ were found to act as Cd transport systems via the cellular membrane. Metallothionein-I/II-null mice are highly susceptible to renal toxicity, hepatotoxicity, bone injury, hematotoxicity and immunotoxicity caused by chronic Cd exposure. Thus, metallothionein plays an important role in detoxification of Cd toxicity.