Abstract
Much recent data supports the “uptake-reduction” model explaining the carcinogenicity of chromium(VI) compounds and the lack of carcinogenicity of chromium(III) com pounds. Cr(VI) readily enters cells by diffusion through a nonspecific anion channel, whereas cells are relatively impermeable to Cr(III). Glutathione appears to facilitate Cr(VI) uptake by reducing Cr(VI) to Cr(III) after it enters the cell, presumably keeping intracellular Cr(VI) concentration low and allowing for further Cr(VI) uptake. Some other nonenzymatic factors, for example, ascorbate and riboflavin, as well as enzymes, such as cytochrome P-450, DT-diaphorase, and the mitochondrial electron transport chain complexes, are capable of reducing Cr(VI) in vitro, but their contribution in vivo is not clear. Cr(VI), once reduced intracellularly, produces various forms of DNA damage including DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, and Cr-DNA adducts. The pathway of Cr(VI) metabolism in different tissues appears to influence the type of “reactive intermediates” produced, for example, Cr(V) and radical species, and thus the nature and extent of DNA damage. This DNA damage presumably accounts for observed functional changes in DNA replication and transcription which may be crucial to the carcinogenicity of chromium(VI) compounds.