Inhibition by rosemary and carnosol of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation.
Extracts of the spice Rosemary officinalis L. have been reported to inhibit experimental carcinogenesis. Two rosemary components, carnosol and ursolic acid, appear to be partly responsible for the antitumorigenic activity of rosemary. The present studies were conducted in order to evaluate the activity of rosemary extract, carnosol and ursolic acid in inhibiting the in vivo formation of mammary 7,12-dimethylbenz[a]anthracene (DMBA)-DNA adducts and the initiation of DMBA-induced mammary tumorigenesis in female rats. Supplementation of diets for 2 weeks with rosemary extract (0.5% by wt) but not carnosol (1.0%) or ursolic acid (0.5%) resulted in a significant decrease in the in vivo formation of rat mammary DMBA-DNA adducts, compared to controls. When injected intraperitoneally (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. Injection of this dose of rosemary and carnosol was associated with a significant 74% and 65% decrease, respectively, in the number of DMBA-induced mammary adenocarcinomas per rat, compared to controls. Ursolic acid injection had no effect on mammary tumorigenesis. Therefore, carnosol is one rosemary constituent that can prevent DMBA-induced DNA damage and tumor formation in the rat mammary gland, and, thus, has potential for use as a breast cancer chemopreventative agent.
Singletary
K
K
Department of Food Science and Human Nutrition, University of Illinois, Urbana 61801, USA.
MacDonald
C
C
Wallig
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D045784:Abietanes; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D010616:Phenanthrenes / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017365:Spices; D014315:Triterpenes / Q000627:therapeutic use; D000097245:Ursolic Acid
D015127:9,10-Dimethyl-1,2-benzanthracene; D045784:Abietanes; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004247:DNA; D018736:DNA Adducts; D010616:Phenanthrenes; D014315:Triterpenes; D000097245:Ursolic Acid; C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; C068623:carnosol