Role of chromium(V), glutathione thiyl radical and hydroxyl radical intermediates in Chromium(VI)‐induced DNA Damage

Abstract

In vitro chromium(VI) is unreactive toward DNA under physiological conditions. Therefore, the ability of chromium(VI) to damage DNA depends on the presence of cellular components capable of forming “reactive intermediates”; upon reaction with chromium(VI). We have examined the role of glutathione and hydrogen peroxide in chromium(VI)‐induced DNA damage in vitro. Reaction of glutathione with chromium(VI) produced significant levels of two chromium(V) complexes and glutathione thiyl radical, whereas reaction of chromium(VI) with hydrogen peroxide produced hydroxyl radical without producing detectable levels of chromium(V). Reaction of DNA with chromium(VI) in the presence of glutathione resulted in Cr‐DNA adducts with little DNA strand breakage. Reaction of DNA with chromium(Vl) in the presence of hydrogen peroxide produced the 8‐hydroxydeoxyguanosine adduct and extensive DNA strand breakage in the absence of significant Cr‐DNA adduct formation. These results suggest that the nature of chromium(VI)‐induced DNA damage will be strongly dependent on the reactive intermediates, i.e. chromium(V) complexes, glutathione thiyl radical and hydroxyl radical, produced by cellular components and systems active in chromium(VI) metabolism.

Key Words:

• chromium‐DNA adducts
• 8‐hydroxydeoxyguanosine
• DNA strand breaks
• spin‐trap
• speciation
• chromium(V)
• EPR‐spectroscopy
• gel electrophoresis

Notes

Presented 13 April 1988 at the 3rd IAEAC Workshop on Toxic Metal Compounds, Follonica, Italy.

To whom correspondence should be addressed at Department of Chemistry, Steele Hall, Dartmouth College, Hanover, New Hampshire 03755 USA.