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| Diane M. Stearns | ||
| Professor | ||
| Department of Chemistry and Biochemistry | ||
| Northern Arizona University | ||
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| Research Interests:
The Stearns laboratory is interested in how metals damage DNA in
ways that may lead to cancer. Current focus is on uranium
and chromium. We are working to identify the DNA lesions formed
by these metals in cultured cells and in vitro, and are
characterizing the mutations caused by these DNA lesions. We are
also interested in the effects of coordinating ligands on metal
uptake, cytotoxicity and genotoxicity. In general, metals can damage DNA by direct or free-radical (indirect) mechanisms.
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Types of lesions arising
from direct metal-mediated damage include: (A)
metal-DNA adducts at bases or the phosphate backbone, (B)
metal-assisted DNA hydrolysis of the phosphate backbone, (C)
DNA-Metal-DNA intrastrand or interstrand crosslinks, and (D)
DNA-Metal-protein crosslinks.
Types of lesions arising from indirect radical-mediated damage include: (E) strand breaks and (F) oxidized bases such as 8-oxodG, and (G) DNA-protein crosslinks. Not all metals will form all types of lesions, and the scheme and explanation above are simplified in that some metals may undergo redox chemistry to form high valent oxo and peroxo species that can produce oxidative DNA damage in the absence of diffusible free radicals.
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