去氢表雄酮抗始发突变作用的研究  

Anti-mutagenicity activity of dehy droepiandrosterone

作　　者：杨笋[1] 付招娣[1] 王芳[1] 曹玉[1] 韩锐[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所药理一室,北京100050

出　　处：《中华肿瘤杂志》2002年第2期137-140,共4页Chinese Journal of Oncology

摘　　要：目的　探讨在肿瘤始发阶段去氢表雄酮 (DHEA)的肿瘤化学预防作用及其机理。方法　通过二甲基苯蒽 [7,12 Dimethylbenz(α) anthracene ,DMBA]诱发的SD大鼠乳腺肿瘤模型和紫外线照射所致DNA损伤和Ames抗突变实验 ,观察DHEA的抗始发突变活性和对化学致癌的抑制作用。结果　DHEA预防给药能够明显抑制DMBA诱发的大鼠乳腺癌 ,对照组在给予DMBA后 8周即可观察到乳腺发生肿瘤 ,至实验结束时 ,肿瘤诱发率为 73.0 % ;DHEA连续给药 12周 ,在 2 5mg/kg剂量组发瘤时间推迟 3.5周 ,肿瘤诱发率降至 2 2 .0 % ,瘤体积较对照组显著减小 ,抑制率达 92 .0 % ,且乳腺肿瘤的潜伏期明显延长 ,至DMBA给药后 11.5周才开始出现瘤块。 10 9mol/LDHEA预处理细胞可对抗紫外线引起的DNA损伤 ,抑制率为 90 .0 %。DHEA对DMBA和苯并芘代谢活化后引起的沙门氏菌TA98和TA10 0的回复突变具有明显抑制作用 ,DHEA 5 μg/平板剂量下的抑制率分别为 5 3.2 %和 73.0 %。此外 ,DHEA在体外可显著抑制细胞内 6 磷酸葡萄糖脱氢酶活性 (P <0 .0 5 ) ,凝胶条带灰度扫描结果表明 ,10 7mol/LDHEA抑制率达 38.6 %。结论　体内外实验结果表明 ,DHEA对肿瘤的始发突变和化学致癌具有明显的抑制作用 ,显示了良好的肿瘤化学预防活性。Objective The chemopreventive activity and mechanism of dehy droepiandrosterone (DHEA)were studied. Methods Model of 7,12 dimethy lbenz (α)anthracene (DMBA) induced breast carcinoma i n Sprague Dawley rats, uitra violet (UV) induced DNA damage and Salm onella mutation assay were used. Results In DMBA induced rat mammary tumor model, the rats were orally given daily DHEA for 2 weeKs before DMBA and continued for 10 weeKs after DMBA administr ation. The results showed significant inhibition of tumor development by DHEA. The incidence of mammary carcinoma also decreased significantly on daily dos e of oral 25 mg/Kg DHEA with the mean tumor volume per rat also remarKably reduced by 92%. Moreover, 25 mg/Kg DHEA treatment c ould significantly increase the carcinoma latency for about 3.5 weeKs as compare d with the control. Using poly merase chain reaction (PCR) assay , in vitro 10 9 mol/L DHEA showed si gnificant inhibitory effect on UV induced DNA damage by 90%. In Ames test, DHEA was found to decrease DMBA and benzo(α)py rene induced TA98 and TA100 His + revertants marKedly and the number of Salmonella clones were significantly reduced by 53.2% and 73.0% on dose of 5 μg DHEA/plate. It was also shown that in vitro 10 7 mol/L DHEA could also effectively inhibit the G 6 PDH activity , which might play an important role in its chemopr ophy laxis activities.Conclusion The results strongly prove that DHEA is a potent cancer chemoprophy laxis agent, which exhibits inhibitory potential on mutation and chemical carcinogen in vivo and in vitro [

关 键 词：去氢表雄酮 抗始发突变作用 乳腺肿瘤 肿瘤 化学预防 

分 类 号：R730.2[医药卫生—肿瘤]