Gilvocarcin V, a Photodynamic DNA Damaging Agent Of Unusual Potency

Rosalie K. Elespuru; Sally A. Look

doi:10.1117/12.942697

19 February 1988 Gilvocarcin V, a Photodynamic DNA Damaging Agent Of Unusual Potency

Rosalie K. Elespuru, Sally A. Look

Proceedings Volume 0847, New Directions in Photodynamic Therapy; (1988) https://doi.org/10.1117/12.942697
Event: Cambridge Symposium on Optics in Medicine and Visual Image Processing, 1987, San Diego, CA, United States

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.

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Rosalie K. Elespuru and Sally A. Look "Gilvocarcin V, a Photodynamic DNA Damaging Agent Of Unusual Potency", Proc. SPIE 0847, New Directions in Photodynamic Therapy, (19 February 1988); https://doi.org/10.1117/12.942697

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