Effect of the Chalcone Analog E,E-bis(2-Hydroxybenzylidene) acetone on the 7,12-Dimethylbenz[a]anthracene-induced Ha-ras Gene Activity In Vivo

Abstract

The chalcone analog E,E-bis(2-hydroxybenzylidene)acetone (HBA) was found to display strong NAD(P)H:quinone reductase (NQO1) inducer potency in Hepa 1c1c7 cells. In order to determine whether this promising chemopreventive activity would extend to anticarcinogenic properties, the effect of HBA on the 7,12-dimethylbenz[a]anthracene (DMBA)-induced expression of the Ha-ras gene in isolated RNA from liver, lung, kidney, spleen, thymus, lymph nodes and bone marrow of CBA/Ca inbred mice was investigated. DMBA is a well-known chemical carcinogen, which can act as initiator by causing point mutations in certain oncogenes and tumor suppressor genes. According to the previous results, elevated Ha-ras expression has been noted even 24 h after DMBA treatment. Administration of HBA simultaneously with DMBA resulted in a decrease of the DMBA-induced Ha-ras gene expression in all the investigated tissues. This observation suggests metabolic interaction of HBA and DMBA. Administration of HBA 24 h prior to the DMBA treatment reduced the Ha-ras gene expression in all the tissues but the liver, where a slight elevation could be detected. This latter effect could be the result of a possible CYP1A inducer and pro-oxidant effects of HBA. The pro-oxidant effect of HBA can be taken into consideration based on its previously demonstrated GSH-reactivity and the present results obtained by investigation of the time-course of Fenton reaction-initiated degradation of 2-deoxyribose in the presence of HBA.