EFFECT OF THE BETA-DIKETONES DIFERULOYLMETHANE (CURCUMIN) AND DIBENZOYLMETHANE ON RAT MAMMARY DNA-ADDUCTS AND TUMORS INDUCED BY 7,12-DIMETHYLBENZ[A]ANTHRACENE

Curcumin is a beta-diketone constituent of the spice turmeric that pos sesses anticarcinogenic properties in several animal models. The prese nt studies were conducted in order to identify beta-diketones structur ally-related to curcumin that would be effective dietary blocking agen ts toward the initiation stage of 7,12-dimethylbenz[a]anthracene (DMBA )-induced rat mammary carcinogenesis. Of the beta-diketone compounds i nitially screened for their capacity to induce quinone-reductase (QR) activity in wild-type Hepa1c1c7 cells and a mutant subclone, curcumin (diferuloylmethane) and dibenzoylmethane were most effective. However, when added to semipurified diets fed to female rats, dibenzoylmethane (1%), but not curcumin (1%), was effective in inhibiting in vivo mamm ary DMBA-DNA adduct formation. This inhibitory effect on mammary adduc t formation was associated with a significant increase in liver activi ties of glutathione S-transferase, QR and 7-ethoxyresorufin-O-deethyla se activities. Female rats provided diets supplemented with dibenzoylm ethane at 0,1, 0.5 and 1.0% for 14 days prior to dosing with DMBA exhi bited a significant decrease in mammary tumor development, compared wi th controls, However, tumor development for animals fed diets containi ng 1.0% curcumin was not different from that of controls. Therefore, d ibenzoylmethane, and possibly other structurally-related beta-diketone s, warrant examination as breast cancer chemopreventative blocking age nts.