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 thatpossesses anticarcinogenic properties in several animal models. The presentstudies were conducted in order to identify beta-diketonesstructurally-related to curcumin that would be effective dietary blockingagents toward the initiation stage of 7,12- dimethylbenz[a]anthracene(DMBA)-induced rat mammary carcinogenesis. Of the beta-diketone compoundsinitially 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, whenadded to semipurified diets fed to female rats, dibenzoylmethane (1%), butnot curcumin (1%), was effective in inhibiting in vivo mammary DMBA-DNAadduct formation. This inhibitory effect on mammary adduct formation wasassociated with a significant increase in liver activities of glutathioneS-transferase, QR and 7-ethoxyresorufin-O-deethylase activities. Femalerats provided diets supplemented with dibenzoylmethane at 0.1, 0.5 and 1.0%for 14 days prior to dosing with DMBA exhibited a significant decrease inmammary tumor development, compared with controls. However, tumordevelopment for animals fed diets containing 1.0% curcumin was notdifferent from that of controls. Therefore, dibenzoylmethane, and possiblyother structurally-related beta-diketones, warrant examination as breastcancer chemopreventative blocking agents.