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藥物食品分析 MEDLINESCIEScopus

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篇名 環境強致癌物7-氯苯幷[a]蔥體外代謝和DNA加成物合成實驗能量限制的影響
卷期 7:1
並列篇名 Effect of Caloric Restriction on in Vitro Metabolism and DNA Binding of the Environmental Potent Tumorigen 7-Chlorobenz[a]Anthracene
作者 邱莉婷詹德進翁榮源符必成Hart,Ronald W.
頁次 23-36
關鍵字 能量限制7-氯苯幷[a]蔥小鼠肝臟微粒體代謝DNA結合Caloric restriction7-chlorobenz[a]anthraceneMouse liver microsomal metabolismDNA bindingMEDLINEScopusSCIE
出刊日期 199903

中文摘要

     環境污染致癌物-7-氯苯幷[a]蔥的代謝和DNA加成物合成實驗中,對所使用的小鼠施予能量限制,取得 9 個月大的雄性 B6C3F1 小鼠和 9 或 12 個月大的雌性 B6C3F1 小鼠之肝臟微粒體,研究其對實驗結果所造成的影響。小鼠從出生開始,以正常飲食飼養;14週後逐步能量限制,到 16 週以餵食正常飲食之 60 %能量;9 個月和 12 個月大處理之,製備得到微粒體。 微粒體和 7- 氯苯幷 [a] 蔥的體外代謝實驗後,所得代謝物經過萃取、逆相高壓液相層析儀純化後, 與標準品比對他們的紫外 - 可見光譜和質譜圖譜後,證明有10 種代謝物,分別如下:反式 -3,4- 二氫二醇 -7- 氯苯幷 [a] 蔥; 反式 -5,6- 二氫二醇 -7- 氯苯幷 [a] 蔥;反式 -8,9- 二氫二醇 -7- 氯苯幷 [a] 蔥;反式 -10,11- 二氫二醇 -7- 氯苯幷 [a] 蔥;反式 -5,6- 環氧 -7- 氯苯幷 [a] 蔥; 和 4-,5-,6-,8-,9- 羥基- 7- 氯苯幷 [a] 蔥。 反式 -3,4- 二氫二醇 -7- 氯苯幷 [a] 蔥的代謝量,正常飲食之微粒體代謝實驗較能量限制者高; 同時,代謝也發生在有公牛胸腺 DNA 的情況下,結果產生修飾的 DNA,藉由32P 後標記後, 薄膜層析和高壓液相層析儀來分離與分析,所有實驗中只發現一個 DNA 加成物, 即是由反式 -3,4- 二氫二醇 -7- 氯苯幷 [a] 蔥衍生的加成物。相同性別和年齡的小鼠中,微粒體合成 DNA 加成物的量,能量限制的較正常飲食者低; 因此, 我們的結果顯示能量限制抑制即將發生之代謝物 - 反式 -3,4- 二氫二醇 -7- 氯苯幷[a] 蔥的形成和明顯地降低其 DNA 加成物的形成。

英文摘要

     The effect of caloric restriction (CR) on the metabolism and DNAbinding of 7-chlorobenz[a]anthracene (7-Cl-BA), a tumorigenic environmentalcontaminant, by liver microsomes of 9-month-old male B6C3F1 mice and 9- and12-month-old female B6C3F1 mice was studied. Mice were fed ad libitum (AL), orstarting at 14 weeks of age, received 60% of the calories consumed by controlmice and were sacrified at 9 or 12 months of age. After microsomal incubations,metabolites were extracted, purified by reversed-phase HPLC, and identified bycomparison of their UV-visible and mass spectral data with those of standards.In each case, ten metabolites were identified: 7-Cl-BA trans-3, 4-dihydrodiol,7-Cl-BA trans-5, 6-dihydrodiol, 7-Cl-BA trans-8, 9-dihydrodiol, 7-Cl-BAtrans-10,11-dihydrodiol, 7-Cl-BA 5,6-epoxide, and 4-,5-,6-,8-,and 9-OH-7-Cl-BA.The quantity of 7-Cl-BA trans-3,4-dihydrodiol was formed in a higher yield fromthe AL microsomes than from the CR microsomes. Metabolism was also performed inthe presence of calf thymus DNA, and the resulting modified DNA was isolated andanalyzed by both 32P-postlabeling/ TLC and 32P-postlabeling/HPLC. Only one DNAadduct, which was derived from 7-Cl-BA trans-3,4-dihydrodiol, was detected inall cases. The levels of adduct formation from CR microsomes were lower thanthose from the AL microsomes of the same sex and same age. Thus, our resultsindicate that CR inhibits the formation of the proximate metabolite, 7-Cl-BAtrans-3,4- dihydrodiol, and significantly reduces the DNA adduct formation.

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