Heavy metals of relevance to human health induce genomic instability

Heavy metals used in medical prostheses or present in water supplies or tobacco can build up in tissues and blood and are well known to produce toxic effects. Normally, legislative controls on the levels of these substances are determined by reference to the acute toxicity data. This paper shows that cadmium and nickel can produce delayed effects in human cells in vitro, which are characteristic of genomic instability. The effects occur even at levels where no acute toxic effects can be demonstrated. Genomic instability can be demonstrated by persistent induction of cytogenetic abnormalities and delayed cell death in progeny of cells many generations after exposure. Formerly, this syndrome has only been definitively proven to occur following irradiation, but in these experiments cell populations exposed for only 1 or 24 hours were expanded over several months, involving eight passages, and the yield of chromosomal aberrations and cell loss due to lethal mutations did not decrease. The consequences of this genomic instability are not yet known but it is possible that many of the systemic symptoms associated with exposure to low concentrations of these metals could involve delayed expression of cellular damage. It is also clear that these effects cannot be predicted from acute toxicity data. Copyright (C) 2001 John Wiley & Sons, Ltd.