The “interceptor” properties of chlorophyllin measured within the three-component system: Intercalator–DNA–chlorophyllin

Abstract

In aqueous solutions, in the presence of double-stranded DNA, chlorophyllin (CHL) forms complexes with each of the three DNA intercalators: acridine orange (AO), quinacrine mustard (QM), and doxorubicin (DOX). The evidence for these interactions was obtained by measurement changes in the absorption and fluorescence spectra of the mixtures containing DNA and intercalators during titration with CHL. A model of simple competition between DNA and CHL for the intercalator was used to define the measured interactions. The concentrations of the complexes estimated based on this model were consistent with the concentrations obtained by actual measurement of the absorption spectra.The present data provide further support for the role of chlorophyllin as an "interceptor" that may neutralize biological activity of aromatic compounds including mutagens and antitumor drugs.

Attenuation of acridine mutagen ICR-191 — DNA interactions and DNA damage by the mutagen interceptor chlorophyllin

“…ICR-191 is an aromatic mutagen having a three-ring structure, it intercalates into DNA and has also mustard-like alkylating properties [30,31]. We expected, therefore, that similar as in the case of intercalators studied by us before [23] CHL will also have the interceptor activity towards ICR-191.…”

“…We have shown for example, that CHL forms complexes with acridine orange, quinacrine mustard and the antitumor drug doxorubicin, with association constants (K a 's) 7.0 × 10 5 , 3.2 × 10 5 and 3.3 × 10 5 M −1 , respectively [22]. Applying experimental analysis to the three-component interactive system: intercalator-DNA-CHL we observed that CHL attenuated binding of these intercalators to DNA thereby showing the interceptor activity [23]. In the present study using similar experimental approach we investigated interactions between the acridine mutagen ICR-191 and DNA in the absence and presence of CHL.…”

“…[41]. The K i association constant and molar extinction coefficient of the DNA-bound intercalator ICR-191 were estimated by the least squares regression analysis as described [23]. Spectral fragments within 360-500 nm have been used in which ICR-191 has absorption band while DNA is not absorbing light.…”

“…Thus, by capturing mutagen molecules CHL neutralizes them preventing their uptake by the cells and subsequent interaction with DNA. It was proposed to define the agents with such properties as the interceptor molecules [21][22][23][24]. Similar to chlorophyllin, caffeine and pentoxifillin were shown to be interceptors of several aromatic compounds such as acridine orange, quinacrine mustard and acridine mutagens ICR-191 and ICR-170, attenuating their mutagenic and cytotoxic effects and preventing interaction with DNA [25][26][27][28][29].…”

“…In prior studies we explored molecular interactions that may be responsible for the interceptor properties of CHL vis-à-vis several intercalators [22,23]. Towards this end using optical spectroscopy we have studied interactions between the intercalators and DNA in the presence and absence of CHL.…”