This review has focused on several parameters related to the delivery of carcinogenic
metal compounds to the cell nucleus as a basis for understanding the intermediates formed between metals and cellular components and the effect of these intermediates on
DNA structure and function. Emphasis has been placed on
metal interactions at the cellular membrane, including lipid peroxidation,
metal interactions with
glutathione and their relation to membrane injury, and
metal effects on the membrane bound
enzyme, Na(+)/K(+)
ATPase.
Metal binding to
metallothionein is also considered, particularly as related to transport and utilization of
metal ions and to genetic defects in these processes exemplified in
Menkes disease. The ability of
cadmium to induce the synthesis of
metallothionein more strongly than
zinc is also discussed in relation to other toxic and carcinogenic metals. The effects of
metal ions on purified
DNA and
RNA polymerase systems are presented with some of the recent studies using
biological ligand-
metal complexes. This review points out the importance of considering how metals affect in vitro systems when presented as ionic forms or complexed to relevant
biological ligands.