Potentiation of genotoxicity by concurrent application of compounds found in betel quid: arecoline, eugenol, quercetin, chlorogenic acid and Mn2+

Abstract 5 components of the betel quid were examined for their clastogenic activities individually and in various combinations. They included the alkaloid, arecoline, from the betel nut ( Areca catechu L.), eugenol, from the betel vine ( Piper betle L.), chlorogenic acid, from tobacco leaves ( Nicotiana tabacum ), quercetin, from fennel seeds ( Foeniculus vulgare Mill.) and the ubiquitous transition metal Mn 2+ . The clastogenic effects of the concurrent applications of arecoline plus eugenol, arecoline plus quercetin and arecoline plus chlorogenic acid were greater than the sum of the action of each individual component. Similarly, the combinations of arecoline, chlorogenic acid and Mn 2+ induced frequencies of chromosome aberrations which exceeded the sum of the clastogenic activities of individually applied compounds or the sum of the clastogenic activities of 2 jointly applied compounds (arecoline plus Mn 2+ , or chlorogenic acid plus Mn 2+ ). The clastogenic activity was estimated as the frequency of metaphase plates with at least 1 chromatid break or chromatid exchange, or the average number of chromatid breaks and exchanges per Chinese hamster ovary (CHO) cell. A potentiating (enhancing) action was also evident when 2 clastogens were used at doses which would not lead to a detectable increase in the frequency of chromosome aberrations when applied individually. It may be useful to distinguish between a “genotoxic range”, which would be applicable to individually assayed compounds, and a “cogenotoxic range”, which may include concentrations at which a chemical exerts a potentiating effect when combined with other genotoxic or non-genotoxic compounds.