Cellular reduction models

The currently known pathways of cellular uptake and metabolism of Cr in different oxidation states are summarized in a modified uptake-reduction model (Fig. 1) (12), initially proposed [for soluble Cr(Vl) compounds] by Wetterhahn and co-workers (170). 

The carcinogenicity of chromium(VI) compounds has been well-documented in epidemiological studies and animal tests Chromium(VI) compounds were mutagenic in bacterial and mammalian cell systems whereas chromium(III) compounds were not active mutagens in the same test systems In subcellular assay systems both chromium(III) and chromium(VI) decreased the fidelity off. Coli DNA polymerase The differences in activity of chromium(VI) compared to chromium(III) in cellular and subcellular systems have been explained in terms of the uptake-reduction model of chromate carcinogenicity ... 

These detailed cell models can be used to study the development in time of processes like myocardial ischaemia (a reduction in coronary blood flow that causes under-supply of oxygen to the cardiac muscle), or effects of genetic mutations on cellular electrophysiology. They allow to predict the outcome of changes in the cell s environment, and may even be used to assess drug actions. 

Figure 21.2 Conceptualized construction of an A-B subunit protein toxin (left). The B chain contains a binding region for docking onto cell surfaces, while the A chain contains a catalytic site that produces cytotoxic affects intracellularly. The two subunits are joined by a disulfide bond that is reductively cleaved at the cellular level to allow the A subunit to affect cell death. A molecular model of ricin is on the right.

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