An investigation into the genotoxic species generated during reduction of chromium(VI) by catechol(amine)s

Abstract

Chromium(VI) is a common occupational carcinogen.¹ The major carcinogenic and mutagenic species are proposed to be Cr(V) and Cr(IV) intermediates formed during the reduction of Cr(VI) to stable Cr(III) compounds,² although indirect evidence suggests that reactive oxygen species (ROS) may also be important.³ The reductions of Cr(VI) by some biological reductants (e.g. ascorbate) have been studied previously, and genotoxic Cr(IV/V) species have been detected.⁴ Another potential reductant in vivo is protein-bound DOPA, which is present on oxidised proteins at low steady-state concentrations prior to enzymatic breakdown.⁵ Recently, we have shown, by EPR spectroscopy, that the reactions of Cr(VI) with model DOPA compounds (catechol(amine)s), and with oxidised proteins themselves, generate several reactive intermediates, including Cr(V) complexes and organic radicals.⁶ Previous studies have proposed that ROS may also be produced during catechol(amine) oxidation.⁷ Here we describe studies of the interaction of DNA with the reactive species produced during the reductions of K₂Cr₂O₇ by catechol(amine)s.