Mechanisms involved in the chemoprevention of flavonoids

Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with Flavone, flavanone, tangeretin. and quercetin were investigated on two steps of aflatoxin B1 (AFB(1))-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of gamma -glutamyl transpeptidase-preneoplastic fuci. In the same conditions of administration, quercetin, a polyhydroxylated flavonoid. showed no protective effect. Moreover, feeding rats with flavanone during the phenobarbital-induced promotion step significantly reduced the areas of placental glutathione S-transferase preneoplastic foci. Quercetin, flavone, and tangeretin, administered in the same conditions, caused no significant effect. Therefore flavanone act as an anti-initiator as well as an anti-promotor. Several mechanisms were involved in the anti-initiating effects of flavone, flavanone. and tangeretin: enhancement of enzymes involved in the detoxication of AFB(1) (glutathione S-transferase, UDP-glucuronyl transferase), increase of the formation of AFB(1)-glulathione conjugates and inhibition of the binding of AFB(1) to DNA. Although the relevance of these data to the human situation remains to be demonstrated, they confirm that several flavonoids administered by the dietary route possess promising chemoprotective effects.