INHIBITION BY ROSEMARY AND CARNOSOL OF 7,12-DIMETHYLBENZ[ALPHA]ANTHRACENE (DMBA)-INDUCED RAT MAMMARY TUMORIGENESIS AND IN-VIVO DMBA-DNA ADDUCT FORMATION

Extracts of the spice Rosemary officinalis L. have been reported to in hibit experimental carcinogenesis. Two rosemary components, carnosol a nd ursolic acid, appear to be partly responsible for the antitumorigen ic activity of rosemary. The present studies were conducted in order t o evaluate the activity of rosemary extract, carnosol and ursolic acid in inhibiting the in vivo formation of mammary 7,12-dimethylbenz[a]an thracene (DMBA)-DNA adducts and the initiation of DMBA-induced mammary tumorigenesis in female rats. Supplementation of diets for 2 weeks wi th rosemary extract (0.5% by wt) but not carnosol (1.0%) or ursolic ac id (0.5%) resulted in a significant decrease in the in vivo formation of rat mammary DMBA-DNA adducts, compared to controls. When injected i ntraperitoneally (i.p.) for 5 days at 200 mg/kg body wt, rosemary and carnosol, but not ursolic acid, significantly inhibited mammary adduct formation by 44% and 40%, respectively, compared to controls. Injecti on of this dose of rosemary and carnosol was associated with a signifi cant 74% and 65% decrease, respectively, in the number of DMBA-induced mammary adenocarcinomas per rat, compared to controls. Ursolic acid i njection had no effect on mammary tumorigenesis. Therefore, carnosol i s one rosemary constituent that can prevent DMBA-induced DNA damage an d tumor formation in the rat mammary gland, and, thus, has potential f or use as a breast cancer chemopreventative agent.