Reaction of chromium(VI) with glutathione or with hydrogen peroxide: identification of reactive intermediates and their role in chromium(VI)-induced DNA damage.

Abstract:

:The types of reactive intermediates generated upon reduction of chromium(VI) by glutathione or hydrogen peroxide and the resulting DNA damage have been determined. In vitro, reaction of chromium(VI) with glutathione led to formation of two chromium(V) complexes and the glutathione thiyl radical. When chromium(VI) was reacted with DNA in the presence of glutathione, chromium-DNA adducts were obtained, with no DNA strand breakage. The level of chromium-DNA adduct formation correlated with chromium(V) formation. Reaction of chromium(VI) with hydrogen peroxide led to formation of hydroxyl radical. No chromium(V) was detectable at 24 degrees C (297 K); however, low levels of the tetraperoxochromium(V) complex were detected at 77 K. Reaction of chromium(VI) with DNA in the presence of hydrogen peroxide produced significant DNA strand breakage and the 8-hydroxydeoxyguanosine adduct, whose formation correlated with hydroxyl radical production. No significant chromium-DNA adduct formation was detected. Thus, the nature of chromium(VI)-induced DNA damage appears to be dependent on the reactive intermediates, i.e. chromium(V) or hydroxyl radical, produced during the reduction of chromium(VI).

authors

Aiyar J,Berkovits HJ,Floyd RA,Wetterhahn KE

doi

10.1289/ehp.919253

subject

Has Abstract

pub_date

1991-05-01 00:00:00

pages

53-62

eissn

0091-6765

issn

1552-9924

journal_volume

92

pub_type

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