Studies Of Cancer Chemopreventive Activity, Mechanism Of Action And Pharmocokinetics Of Curcumin Derivative 91022

3,4-Dihydroxychalcone (91022), a new curcumin derivative was developed by our institute. The cancer preventive activity, mechanism of action of curcumin derivative 91022 and its pharmacokinetics were studied in this thesis.Three models were used in the chemopreventive activity studies. (1) Two-stage chemically-induced transformation of Balb/3T3 cell in vitro. It was shown that 91022 significantly inhibited 3-methylcholanthrene(3-MCA) and TPA induced malignant transformation of Balb/3T3 cells. (2) 7,12-dimethylbenz(a)anthraene (DM BA) and croton oil-induced mouse skin papilloma. It was demonstrated that 91022 could inhibit DMBA/croton oil induced mouse skin papilloma, which include prolonging the latent period of tumor occurrence, decreasing the incidence of papilloma and reducing tumor number per mouse in dose-dependent manner. (3) 4-NQO induced malignant progression of tumors induce by DMBA/croton oil. Histophathology showed that 91022 could reduced the malignant degree of tumors. The above experimental results suggested that 91022 is a potent cancer preventive agent in vitro as well as in vivo.91022 exhibited a significant inhibition on cyclophosphamide(CTX)-induced micronucleus formation of polychromatic erythrocytes (PCE) of bone marrow in mice.. In Ames test, 91022 could decrease MMS-induced TA100 and DNR- induced TA98 his+-revertants. Unscheduled DNA synthesis(UDS) representes ca-...