第7卷‧第3期,
198307
, pp. 379-386
黃麴毒醇抑制大白鼠肝臟細胞核核酸合成之機制
- 作者:
陳淑真; 林明美; 鍾明芳
- 作者服務機構:
國立陽明醫學院生化學科及生化研究所
- 中文摘要:
黃麴毒醇為黃麴毒素B代謝物中,變異性及致癌性最強者。它會很快抑制大白鼠肝臟細胞核RNA之合成。當大白鼠經腹腔注射黃麴毒醇(0.4毫克/100公克體重)2小時後,肝臟細胞核RNA總合成量降低68.2%,細胞核之RNA合成酵素活性則降低51.7%。離體實驗顯示黃麴毒醇並不直接抑制RNA合成酵素之活性。若加入-Amanitin(3微克/毫升)於反應液中以抑制RNA合成酵素乙,則不受-Amanitin抑制之合成酵素活性只被降低26%,但被-Amanitin抑制之合成酵素活性被黃麴毒醇抑制71.4%。進一步用DEAF-Sephadex A-25柱體層析證明黃麴毒醇主要抑制RNA合成酵素乙之活性,合成酵素丙稍微受抑制,合成酵素甲則不受影響。黃麴毒醇亦降低肝臟細鮑核內DNA之模板功能。在適當量的DNA濃度下,DNA的模板功能被抑制程度高達40%。這些結果表示黃麴毒醇之抑制RNA合成乃由於干擾了細胞核RNA合成酵素之活性以及損害了細胞核DNA之模板功能。
- 英文摘要:
Aflatoxicol, the most mutagenic and carcinogenic metabolite of mycotoxin aflatoxin B 1, is able toinhibit rapidly the liver nuclear RNA synthesis of Sprague-Dawley rat. Two hours after i.p. injection ofaflatoxicol (0.4 mg/100g body weight), the total rat liver nuclear RNA synthesis assayed in vitro was re-duced 68.2% and the activity of total RNA polymerases solubilized from liver nuclei was reduced 51.7%.In vitro experiment demonstrated that aflatoxicol did not inhibit RNA polymerases activity directly. Inthe presence of -amanitin at the concentration of 3 μg/ml inhibiting RNA polymerase II activity, the-amanitin resistant activity exhibited by solubilized RNA polymerases was inhibited only 26%, however-amanitin sensitive activity was inhibited 71.4% by aflatoxicol. Further chromatography on DEAE-Sephadex A-25 column demonstrated that the activity of RNA polymerases II was preferentially inhibited,and RNA polymerase III was slightly inhibited, whereas RNA polymerase I was not affected. The livertotal nuclear DNA isolated from rats after AFL treatment exhibited lower template activity. When assayedwithin suitable concentration range of nuclear DNA, the template activity was reduced approximately 40%by aflatoxicol. These results suggest the inhibition of rat liver nuclear RNA synthesis by aflatoxicol is dueto combined effects of interference with RNA polymerases activity and the impairment of DNA templatefunctions.
- 中文關鍵字:
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- 英文關鍵字:
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