- 作者: 林仁混;邵作賢
- 作者服務機構: 國立臺灣大學醫學院生化學科
- 中文摘要: 環腺嘌呤核?酸二酯?(Cyclic AMP phosphodiesterase)係控制細胞中Cyclic AMP濃度之重要??之一。由於細胞中Cyclic AMP之含量可以調節細胞的形狀、運動、粘著性、生長速率及巨分子的合成。因此學者們認為Cyclic AMP與致癌物之作用可能有密切的關係。 本研究探討致癌性阿脞色素(N'-AcMADAB)對鼠肝細胞中Cyclic AMP phosphodiesterase活性之影響。當老鼠餵以N'-AcMADAB (1 m mole/kg)後,該?之活性很快增高,至第五星期後達到最高峰,接著降下至最低峰,再恢復到正常的活性。在初期的增高作用甚為特殊,因為僅餵以正常飼料之動物並無此作用。根據文獻的記載,推論肝細胞遭受致癌性阿脞色素之攻擊,可能首先引起細胞內Cyclic AMP之減少,接著才啟動癌瘤之轉化(Neoplastic transformation)。 Cyclic AMP phosphodiesterase之增高作用,可能由活化後之致癌性色素與細胞中之基因組(Genome)交互反應後之結果。至於Cyclic AMP在癌化作用(Carcinogenesis)之步驟上佔有何種角色至今未明。當前之重要課題將是探討細胞中Cyclic AMP之降低如何推動癌瘤之轉化,其詳細之機轉,值得進一步之探討。
- 英文摘要: Cyclic AMP Phosphodiesterase is one of the key enzymes for controlling the level of intracellular cyclic AMP which regulates cell shape, motility, adhesiveness to substratum, growth rate and the synthesis of macromolecules in several cell lines. The livers of rats that were fed carcinogenic aminoazo dye (N'-AcMADAB) showed an elevation of cyclic AMP phosphodiesterase up to 5 weeks, after then the activity of the enzyme declined to a lower level and finally returned to the normal level. The appearance of the elevation phase in dye-treated rat is quite specific since the level of the enzyme in control animals that received basal diet alone do not change. It is probable that the content of intracellular cyclic AMP in the hepatic cells exposed to the azo dye carcinogen may be depleted, resulting in induction of a series of metabolic aberration which lead neoplastic transformation. The elevation of cyclic AMP phosphodiesterase may be explained as the consequence of the interaction of the metabolically activated carcinogen with the relevant genome. The exact role of cyclic AMP in the process of carcinogenesis is not clear, therefore, the crucial problem ahead is to elucidate the molecular mechanism of neoplastic transformation induced by cellular cyclic AMP depletion.
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