Nucleic Acids Research, Vol 26, Issue 7 1588-1596, Copyright © 1998 by Oxford University Press
RN Bose, BS Fonkeng, S Moghaddas and D Stroup
Reactions of bis(2-ethyl-2-hydroxy-butanato)oxochromate(V) with pUC19 DNA,
single-stranded calf thymus DNA (ss-ctDNA), a synthetic oligonucleotide,
5'-GATCTATGGACTTACTTCAAGGCCGGGTAATGCTA-3' (35mer), deoxyguanosine and
guanine were carried out in Bis-Tris buffer at pH 7.0. The plasmid DNA was
only nicked, whereas the single-stranded DNA suffered extensive damage due
to oxidation of the ribose moiety. The primary oxidation product was
characterized as 5-methylene-2-furanone. Although all four bases (A, C, G
and T) were released during the oxidation process, the concentration of
guanine exceeds the other three. Orthophosphate and 3'-phosphates were also
detected in this reaction. Likewise, the synthetic oliogomer exhibits
cleavage at all bases with a higher frequecncy at G sites. This increased
cleavage at G sites was more apparent after treating the primary oxidation
products with piperidine, which may indicate base oxidation as well. DNA
oxidation is shown to proceed through a Cr(V)-DNA intermediate in which
chromium(V) is coordinated through the phosphodiester moiety. Two
alternative mechanisms for DNA oxidation by oxochromate(V) are proposed to
account for formation of 5-methylene-2-furanone, based on hydrogen
abstraction or hydride transfer from the C1' site of the ribose followed by
hydration and two successive beta-eliminations. It appears that phosphate
coordination is a prerequisite for DNA oxidation, since no reactions
between chromium(V) and deoxyguanosine or guanine were observed. Two other
additional pathways, hydrogen abstraction from C4' and guanine base
oxidation, are also discussed.
ARTICLES
Mechanisms of DNA damage by chromium(V) carcinogens
Department of Chemistry, Kent State University, Kent, OH 44242, USA. rbose@Platinum.kent.edu
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