Photoaddition to DNA by Nonintercalated Chlorpromazine Molecules

Irene E. Kochevar, Carmelo Garcia, Nicholas Geacintov

Research output: Contribution to journalArticle

Abstract

Chlorpromazine (CPZ) forms photoadducts with DNA and photosensitizes DNA strand breaks. These reactions may be responsible for the reported photomutagenicity of CPZ and for the well-known cutaneous and ocular phototoxicity associated with this drug. We have investigated whether CPZ molecules that are intercalated between base pairs in double-stranded (ds) DNA are the absorbing species for the photoaddition reaction. Quenching of CPZ fluorescence by ds-DNA gave nonlinear Stern-Volmer plots, indicating that more than one type of complex is formed. Linear dichroism spectra of CPZ in the presence of ds-DNA showed a minimum at 345 nm, indicating that the absorption maxima of intercalation complex(es) are red-shifted compared to the absorption maximum of free CPZ at 307 nm. The sum of the absorption of all CPZ complexes with ds-DNA, obtained from dialysis experiments, was broadened and maximized at about 315 nm, indicating that complexes not involving intercalation dominate the absorption spectrum at λ < 350 nm. The wavelength dependence for covalent binding of CPZ to DNA was determined by irradiating 3H-CPZ in the presence of ds-DNA at 310, 322, 334, 346, 358 and 370 nm. The resulting spectrum correlated closely with the absorption spectrum of nonintercalated CPZ rather than with the spectrum of intercalated CPZ, indicating that the latter species is not the chromophore for the photoaddition reaction.

Original languageEnglish (US)
Pages (from-to)692-697
Number of pages6
JournalPhotochemistry and Photobiology
Volume68
Issue number5
StatePublished - Nov 1998

Fingerprint

chlorpromazine
Chlorpromazine
deoxyribonucleic acid
Molecules
DNA
molecules
Intercalation
intercalation
Absorption spectra
Phototoxic Dermatitis
absorption spectra
dialysis
DNA Breaks
Dialysis
Chromophores
Base Pairing
strands
chromophores
dichroism
Quenching

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Photoaddition to DNA by Nonintercalated Chlorpromazine Molecules. / Kochevar, Irene E.; Garcia, Carmelo; Geacintov, Nicholas.

In: Photochemistry and Photobiology, Vol. 68, No. 5, 11.1998, p. 692-697.

Research output: Contribution to journalArticle

Kochevar, Irene E. ; Garcia, Carmelo ; Geacintov, Nicholas. / Photoaddition to DNA by Nonintercalated Chlorpromazine Molecules. In: Photochemistry and Photobiology. 1998 ; Vol. 68, No. 5. pp. 692-697.
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