Alleviation of mutagenic effects of polycyclic aromatic agents (quinacrine mustard, ICR-191 and ICR-170) by caffeine and pentoxifylline

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

“…This mechanism of protection is known as "interceptor" mode of CAF and other methylxanthines action and was proposed by Bedner et al [19]. 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.…”

“…This problem can be overcome by using thermodynamical models of mixed aggregation, which allow for infinite homo-and heterocomplexation between interacting aromatic molecules and enable one not only to calculate binding constants, that is, neighborhood association constants, but also to determine concentrations of each possible component of every analyzed mutagen-interceptor mixture. Such approach was successfully applied for interaction analyses of HCAs [15] and other aromatic molecules [22,35,36] with caffeine and other methylxanthines and will be discussed in detail in the next section of this paper.…”

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

“…The association constant, within the limits of the estimation errors, is high (2.8 × 10 5 M − 1 ±0.5 × 10 5 M − 1 ) when compared with complexes of other compounds considered as the interceptors with the mutagens. Thus, for example, the xanthines caffeine and pentoxifillin interact with ICR-191 and ICR-170 mutagens with association constants about 10 1 M −1 [28]. The association constant in the interaction between acridine orange and caffeine is 2 × 10 2 M −1 [42].…”

“…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].…”

Quantitative correlation of the in vitro biological effect with parameters of molecular complexation in mutagen-interceptor systems

“…However, to date one more set of biological data, well matching the basic postulates of the IPA theory, has been accumulated, viz. the antimutagenic action of the interceptor molecules towards aromatic mutagens in bacteria cell systems (see for review Piosik et al (2003); Woziwodzka et al (2011);Dashwood and Guo (1993) In the present letter we aim to testify the existence of quantitative link between the biological and physico-chemical parameters in mutagen-interceptor systems based on the IPA theory.…”