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 (AFB1)-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 foci. 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 AFB1 (glutathione S-transferase, UDP-glucuronyl transferase), increase of the formation of AFB1-glutathione conjugates and inhibition of the binding of AFB1 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.
Siess
M H
MH
Unité de Toxicologie Nutritionnelle, Institut National de la Recherche Agronomique, Dijon, France. siess@dijon.inra.fr
Le Bon
A M
AM
Canivenc-Lavier
M C
MC
Suschetet
M
M
D016604:Aflatoxin B1 / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000378:metabolism; D018890:Chemoprevention; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D004032:Diet; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage; D011794:Quercetin / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D044950:Flavanones; D047309:Flavones; D005419:Flavonoids; D004247:DNA; D011794:Quercetin; D016604:Aflatoxin B1; D005978:Glutathione; C059006:tangeretin; C043562:flavone; C028610:flavanone; D010634:Phenobarbital