Preliminary studies from this laboratory indicated that feeding 1% dibenzoylmethane (DBM) in the diet has an exceptionally potent inhibitory effect on 7,12 dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sencar mice. Feeding 1% DBM in the diet to C3H/OuJ mice completely (100%) inhibits estrogen-dependent formation of spontaneous breast tumors. In additional studies, feeding 1% DBM in the diet to intact female Sencar mice inhibits proliferation of the mammary gland and uterus as determined by the bromodeoxyuridine (BrdUr) labeling index and uterine wet weight during the estrous phase of the estrous cycle. Additional preliminary studies indicate that feeding 1% DBM in the diet to mice induces increased levels of hepatic cytochromes P-450 as well as increased hepatic hydroxylation and glucuronidation of estradiol. We plan to confirm our preliminary data and to test the hypothesis that DBM inhibits DMBA-induced breast carcinogenesis and spontaneous breast carcinogenesis by antagonizing estrogen action at receptor levels and by inducing phase I and phase II enzymes for carcinogen and estrogen metabolic inactivation. We also plan to test our hypothesis that dietary DBM will inhibit the growth of estrogen-inactivation. We plan to t est our hypothesis that dietary DBM will inhibit the growth of estrogen- dependent breast tumors in Balb/c athymic mice. Our Specific Arms are: (1) to study the dose-response effects of DBM on DMBA-induced mammary carcinogenesis and spontaneous breast cancer in mice and to determine the effects of DBM when it is given at different stages of carcinogenesis (during the initiation, the post initiation or during the growth of breast tumors), (2) to elucidate the effects of dietary DBM on the estradiol mitogenic action and estradiol metabolism, and the effect of DBM as a potential inhibitor of estradiol binding to its receptors will also be evaluated, (3) to elucidate the effects of dietary DBM as a potential inhibitor of estradiol binding to its receptors will also be evaluated, (3) to elucidate the effects of dietary DBM on the formation of mammary gland DNA-[3H]DMBA adducts and DMBA metabolism by liver microsomes. Our proposed studies will provide information on the potency of dietary DBM and on the mechanisms of its inhibitory action on chemically-induced breast carcinogenesis and the formation of spontaneous breast cancer in mice. This project should also provide information on whether or not DBM could be a potentially valuable agent for breast cancer prevention as well as for possible effects on breast cancer growth.
| Lin, C C; Ho, C T; Huang, M T (2001) Mechanistic studies on the inhibitory action of dietary dibenzoylmethane, a beta-diketone analogue of curcumin, on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis. Proc Natl Sci Counc Repub China B 25:158-65 |
| Huang, M T; Lou, Y R; Xie, J G et al. (1998) Effect of dietary curcumin and dibenzoylmethane on formation of 7,12-dimethylbenz[a]anthracene-induced mammary tumors and lymphomas/leukemias in Sencar mice. Carcinogenesis 19:1697-700 |
