Addition of DNA to CrVI and Cytochrome b5 Containing Proteoliposomes Leads to Generation of DNA Strand Breaks and CrIII Complexes

摘要: Chromium (Cr) is a cytotoxic metal that can be associated with variety of types DNA damage, including Cr-DNA adducts and strand breaks. Prior studies purified human cytochrome b(5) NADPH:P450 reductase in reconstituted proteoliposomes (PLs) demonstrated rapid reduction Cr(VI) (hexavalent chromium, as CrO(4)(2-), the generation Cr(V), superoxide (O(2)(*-)), hydroxyl radical (HO(*)). Studies reported here examined potential for species produced by this system to interact DNA. Strand breaks plasmid increased over time aerobically, but were not observed absence O(2). Cr(V) formed under both conditions, so are mediated directly Cr(V). The aerobic significantly prevented catalase EtOH, chelator diethylenetriaminepentaacetic acid (DTPA), suggesting they largely due HO(*) from Cr-mediated redox cycling. EPR was used assess formation complexes. Following 10-min incubation PLs, DNA, intense signals at g=5.7 g=5.0 observed. These attributed specific Cr(III) complexes large zero field splitting (ZFS). Without g=5 region weak. ZFS seen, when Cr(III)Cl(3) incubated Cr(III)-DNA interactions different generated PLs. After 24 h, broad signal g=2 small ZFS. This without it seen plasmid. It concluded detect depend on presence manner which formed.