| Summary: | 碩士 === 中國醫藥學院 === 中國醫學研究所 === 89 === (-)-Epigallocatechin gallate (EGCG) and ellagic acid (EA), plant polyphenolic compounds, have been showen to have anticarcinogenic and antimutagenic effects in several biologic systems. However, more studies are needed to understand their underlined mechanisms. DNA adducts and mutations are considered as early indictors in the pathogenesis of carcinogenesis. In this study, we developed an animal model to investigate the protective effects of EGCG and EA on genotoxicant-induced DNA damage and mutations. Mice were orally fed with EGCG or EA for 7 days before challenging with genotoxicant N-ethyl N-nitrosourea (ENU). Two hours after ENU administration, mice were sacrificed, and the liver DNA was extracted for analysis of DNA adduct (7-ethylguanine) by using highly sensitive and specific gas chromatography/mass spectrometry (GC/MS). Another sets of mice were sacrificed 5-6 weeks after ENU administration; the splenic lymphocytes were isolated and cultured in the presence of the selective agents 6-thioguanine. The mutant colonies were counted to determined hprt mutation frequency. The level of 7-EG in the liver tissues of 30 mg/kg ENU-exposed mice was 53 ± 9 pmol/μmol guanine, much higher than that in the negative control mice (<1 pmol/μmol guanine). Pretreatment with EGCG (100 and 200 mg/kg) or EA (200 mg/kg) significantly reduced ENU-induced 7-EG in mouse liver tissues (P<0.05). Treatment with 30,60, and 90 mg/kg ENU in mice induced the hprt mutant frequencies of 36 ± 15 ×10-6,63 ± 12 ×10-6 and 114 ± 20 ×10-6, respectively, as compared to the negative control (2.0 ± 0.3 ×10-6). Pretreatment with EGCG (25,100 and 200 mg/kg) or EA (100 and 200 mg/kg) significantly reduced ENU-induced hprt mutations in mice (P<0.05). Our data showed EGCG and EA could reduce ENU-induced DNA damage and hprt mutations, suggesting that the anticarcinogenic effects of EGCG and EA might at least partly result from this mechanism.
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