Natural Compounds in the Human Diet and their Ability to Bind Mutagens Prevents DNA–Mutagen Intercalation

Abstract

Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.

Heterocyclic Aromatic Amines Heterocomplexation with Biologically Active Aromatic Compounds and Its Possible Role in Chemoprevention

“…The "interceptor" mode of CAF was described and analyzed for HCAs [15] and several other aromatic compounds: ethidium bromide [20,21], propidium iodide [19,20], quinacrine mustard, ICR170, ICR191 [22], proflavine [23], and several anticancer drugs [17,24,25]. Similar mechanism was also described for interaction of chlorophyllin (CHL) [26] and other natural constituents of human diet [27] with several aromatic compounds. It was demonstrated that CHL forms stacking heterocomplexes with HCAs and in consequence diminishes their mutagenic activity and reduces their absorption from gastrointestinal tract [28,29].…”

“…The latter mechanism, as described before, reduces mutagenic potential of aromatic mutagens by formation of molecular complexes with aromatic mutagens, thus reducing their bioavailability. Such effects were described for one of the model mutagens, acridine orange, and resveratrol by Osowski et al [27].…”

Hetero-association of aromatic molecules in aqueous solution

“…Hetero-association in Drug-xanthine systems has been extensively studied by NMR, UV-vis, Fluorescence spectroscopies, titration microcalorimetry, partitioning in waterorganic mixture, molecular modelling and other techniques for the following aromatic drugs: daunomycin (DAU) [127,[133][134][135][136], doxorubicin (DOX) [33,42,127,[137][138][139], actinomycin D (AMD) and its derivatives [133,[140][141][142][143], benzene and its derivatives [122,144], novantrone/mitoxantrone (NOV) [42, 127, 135-137, 145, 146], nogalamycin (NOG) [138], norfloxacin (NOR) [135,136,147], camptothecins [139,148,149], quinoxaline [84], chloroquine [84], DAPI [150], phenothiazines [121,151,152], riboflavin [135,[153][154][155], porphyrins [156,157], acridine mutagens [53,54,124,125,[133][134]…”

“…It was concluded that complexation of aromatic ligands with xanthines results from π-π stacking at pH close to neutral, which is based on systematic NMR magnetic shielding of aromatic protons of xanthine (or a drug) on increasing the concentration of the drug (or a xanthine) [115, 122, 133-135, 138, 145, 147, 149, 163], on specific changes in absorption of the drug in the visible range of the spectrum (hypochromic and bathochromic shifts) on increasing the concentration of xanthine [42, 53, 54, 124, 128, 137, 150-152, 157, 159] and on red-shifts in the absorption/emission bands in fluorescence [53,137,140,157]. The overwhelming majority of published NMR work on hetero-association reports that π-stacking affects the value of chemical shift, except in a few very rare examples, e.g.…”

“…The effect of hetero-association in certain combinations of aromatic drugs is currently considered to be a potential strategy for the regulation of the medico-biological activity of aromatic drugs in clinical practice, e.g. in reduction of the consequences of overdosing of drugs during chemotherapy [42,52] or in the production of antimutagenic effects in vivo [53][54][55]. The recent in vitro study of cellular effects of a mixture of doxorubicin with fullerene [56], complemented by physico-chemical investigation of their complexation in physiological media [57,58], has shown that the effect of hetero-association may potentially lie behind new applications of fullerene molecules as elements of combinational chemotherapy of cancer.…”