Inhibition by dietary dibenzoylmethane of mammary gland proliferation, formation of DMBA-DNA adducts in mammary glands, and mammary tumorigenesis in Sencar mice.
Dibenzoylmethane (DBM) is a minor constituent of licorice and a beta-diketone analogue of curcumin. Feeding 1% DBM in the diet to Sencar mice during both the initiation and the post-initiation periods strongly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor multiplicity and mammary tumor incidence by 97%. In further in vivo studies to elucidate the possible mechanisms of the inhibitory action of DBM, feeding the 1% DBM in the AIN-76A diet to immature Sencar mice for 4-5 weeks decreased the uterine wet weight by 43%, inhibited the proliferation rate of mammary gland epithelial cells by 53%, uterine epithelium by 23%, and uterine stroma by 77%, when mice were killed during the first estrus phase of estrous cycle. In addition, feeding 1% DBM in the diet to Sencar mice at 2 weeks before, during and 1 week after DMBA treatment (intubation of 1 mg DMBA per mouse once a week for 5 weeks) inhibited formation of total DMBA-DNA adducts in mammary glands by 72% using a post-32P-labeling assay. Thus, feeding 1% DBM diet to Sencar mice inhibited formation of DMBA-DNA adducts in mammary glands and lowered the proliferation rate of the mammary gland in vivo. These results may explain the strong inhibitory actions of dietary DBM on mammary carcinogenesis in mice.
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Laboratory for Cancer Research, College of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
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MacDonald
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Huang
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D002455:Cell Division / Q000187:drug effects; D047188:Chalcones; D018736:DNA Adducts / Q000096:biosynthesis*; D004032:Diet; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D018632:Mice, Inbred SENCAR; D009929:Organ Size / Q000187:drug effects; D014599:Uterus / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects
C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D016588:Anticarcinogenic Agents; D001565:Benzoates; D002273:Carcinogens; D047188:Chalcones; D018736:DNA Adducts; D015127:9,10-Dimethyl-1,2-benzanthracene; C061481:dibenzoylmethane