In Vivo Inhibition of Mammary Carcinogenesis, Formation of DNA-Carcinogen Adducts, and Mammary Proliferation by Dietary Dibenzoylmethane

摘要

Dibenzoylmethane (DBM) is a minor constituent in licorice and has anti-inflammatory activity. Feeding 1% DBM in the diet to Sencar mice during both the initiation and post-initiation stages strongly inhibited 7,12-dimethylbenz[a]-anthracene (DMBA)-induced mammary tumorigenesis in both tumor incidence and tumor multiplicity. Feeding 1% DBM in the diet to immature mice for 4-5 weeks decreased uterine wet weight, inhibited proliferation of uterus and mammary gland, and lowered serum estradiol levels. In addition, feeding 1% DBM in the diet to mice increased liver weight and levels of hepatic cytochrome P-450 as well as increased hepatic hydroxylation and glucuronidation of estradiol. In further studies, feeding 1% DBM in the diet to mice at 2 weeks before, during and for a week after DMBA treatment (intubation of 1 mg DMBA in corn oil per mouse once a week for 2 or 5 weeks) markedly inhibited formation of mammary gland DMBA-DNA adducts by a [~(32)P]post-labeling assay. Adding various doses of DBM to an incubation of DMBA with mouse liver microsomes in vitro inhibited DMBA metabolism and formation of DMBA-DNA adducts in a dose-dependent manner. In an assay of competitive binding to estrogen receptors with [~3H]estradiol in vitro, DBM showed only weak binding affinity.