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Proceedings Paper

Gilvocarcin V, a Photodynamic DNA Damaging Agent Of Unusual Potency
Author(s): Rosalie K. Elespuru; Sally A. Look
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Paper Abstract

Gilvocarcin V (GV) is a planar, aromatic DNA-intercalating C-glycoside isolated as a natural product antibiotic. In the presence of UVA or visible radiation, it becomes a DNA damaging agent at low doses in both bacterial and mammalian cells. In mice treated without regard to light exposure, GV exhibited antitumor activity at high doses, with little accompanying toxicity. Wavelength-dependence studies showed that lambda prophage induction profiles were similar to (part of) the absorption spectrum of GV, with a peak near 400 nm. However, significant induction at a higher wavelength (546 nm), was observed at relatively high (e.g. 1 μg/m1) concentrations of GV. The DNA damaging activity of GV was dependent on both the concentration of antibiotic and the fluence of radiation in a reciprocal manner. Mutagenesis and DNA binding experiments suggest a preference for interaction with AT-rich regions of DNA, but multiple modes of interaction seem likely. The presence of different C-glycosides on the gilvocarcin V chromophore may alter the pharmacological properties of the molecule, but photoactivation appears to be independent of these groups. The therapeutic possibilities of gilvocarcins remain largely unexplored; the demonstrated potency of these compounds when activated, the reciprocity effect, possibility of structural variation, and apparent lack of toxicity in mammalian systems are properties which could be exploited in therapeutic development.

Paper Details

Date Published: 19 February 1988
PDF: 9 pages
Proc. SPIE 0847, New Directions in Photodynamic Therapy, (19 February 1988); doi: 10.1117/12.942697
Show Author Affiliations
Rosalie K. Elespuru, Laboratory of Chemical and Physical Carcinogenesis (United States)
Sally A. Look, Laboratory of Chemical and Physical Carcinogenesis (United States)

Published in SPIE Proceedings Vol. 0847:
New Directions in Photodynamic Therapy
Douglas C. Neckers, Editor(s)

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