INDUCTION OF AN ADAPTIVE RESPONSE TO QUERCETIN, MITOMYCIN-C AND HYDROGEN-PEROXIDE BY LOW-DOSES OF QUERCETIN IN V79 CHINESE-HAMSTER CELLS

The adaptive response is a phenomenon by which cells exposed to low, n on-cytotoxic doses of a genotoxicant become significantly resistant to a subsequent higher dose of the same or another genotoxic agent, Indu ction of the adaptive response has been mainly studied using ionizing radiation and alkylating agents as genotoxic agents. However, other mu tagenic agents may warrant further study, since the adaptive response as a whole may be an important general biological mechanism to maintai n genetic integrity and thus could prevent carcinogenic initiation of cells. The exposure to mutagenic agents present, or formed, in the die t is considered an important factor in the etiology of human tumors an d a considerable number of these agents have not yet been identified o r characterized, Flavonoids are a large group of polyphenolic quinoids found in a wide variety of edible fruits and vegetables and a few, su ch as quercetin, present genotoxic activity in vitro. The mechanisms o f mutagenicity of quercetin involve the production of oxygen radicals through an autoxidation process dependent on pH value and the presence of oxygen, Although there are few doubts regarding the mutagenicity o f quercetin in vitro, carcinogenicity of this flavonoid is still contr oversial. In view of these conflicting results and the radiomimetic na ture of the mutagenicity of flavonoids, we addressed the question of c ell exposure to quercetin at the low levels present in the diet leadin g to adaptation to further exposure to mutagens or carcinogens. The wo rk reported here concerns induction of an adaptive response by low dos es of quercetin to challenging doses of quercetin and other compounds, namely hydrogen peroxide and mitomycin C, using induction of chromoso mal aberrations in V79 cells as the end point.