Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Thermodynamic Stability of a DNA Duplex Containing a Spiroiminodihydantoin Lesion

Chromium(VI) is well established as a potent carcinogen. Inside the cell Cr(VI) is reduced to Cr(III) generating high valent Cr(V) and Cr(IV) compounds as well as carbon- and oxygen-based radicals. These species can oxidatively damage DNA producing base lesions and strand breaks. Hexavalent Cr produces both 7,8-dihydro-8-oxoguanine (8-oxoG) and spiroiminodihydantoin (Sp) lesions, with Sp adducts being present in amounts at least 10-20 times greater than 8-oxoG (1, 2). In this study, the thermodynamic stability of a 15-mer DNA duplex containing an Sp lesion is examined using spectroscopic techniques and differential scanning calorimetry. The enthalpies, entropies and free energies of duplex formation for the 15-mer containing guanine, 8-oxoG and Sp are compared and discussed in relation to how the presence of this lesion could affect cellular processes.

References and Footnotes
  1. Slade, P. G., Hailer, M. K., Martin, B. D., and Sugden, K. D. (2005) Guanine-specific oxidation of double-stranded DNA by Cr(VI) and ascorbic acid forms spiroiminodihydantoin and 8-oxo-2'-deoxyguanosine. Chem. Res. Toxicol. 18, 1140-1149.
  2. Hailer, M. K., Slade, P. G., Martin, B. D., and Sugden, K. D. (2005) Nei deficient Escherichia coli are sensitive to chromate and accumulate the oxidized guanine lesion spiroiminodihydantoin. Chem. Res. Toxicol. 18, 1378-1383.

Fadzai Chinyengetere and
Elizabeth R. Jamieson*

Department of Chemistry, Smith College, Northampton, MA 01063

*Phone: 413-585-7588
Fax: 413-585-3786
Email: ejamieso@email.smith.edu