Stimulation of ornithine decarboxylase activity and DNA synthesis by phorbol esters or bile acids in rat colon.
Stimulation of ornithine decarboxylase activity and DNA synthesis by phorbol esters or bile acids in rat colon.
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DOI：
10.20772/cancersci1959.75.1_29
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
S. Takano;M. Akagi;G. Bryan
中科院分区：
文献类型：
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作者：
S. Takano;M. Akagi;G. Bryan
研究了雄性非近交系大鼠直肠内给予肿瘤促进剂12-O-十四烷酰佛波醇-13-乙酸酯(TPA)或各种胆汁酸后结肠上皮鸟氨酸脱羧酶(ODC)活性和DNA合成的变化。单次滴注 TPA，剂量低至 16 nmol，导致结肠 ODC 活性显着（约 10 倍）增加。在 4 小时观察到 ODC 活性峰值，直肠内 TPA 后约 24 小时酶活性恢复到对照水平。该模式与脱氧胆酸钠处理后观察到的几乎相同。 TPA 显示出比脱氧胆酸盐更有效的 ODC 活性诱导，尽管在脱氧胆酸盐处理的情况下最大诱导更大。经过 4-12 小时的初始抑制后，TPA 和脱氧胆酸盐均在直肠内滴注后 2 天刺激 DNA 合成。对 26 种胆汁酸的结构-活性研究表明，在 3α、7α、12α 位置中的两个位置具有 α-羟基的 5β-胆烷酸和具有 3α-羟基的 5β-胆烷酸显着诱导结肠 ODC 活性，而 3α、6α-二羟基酸则没有。用酮基取代羟基或从 α 构型变为 β 构型会降低 ODC 诱导活性。三取代的 5β-胆烷酸衍生物，无论是羟基还是酮基，都不会刺激 ODC。这些数据表明，具有明确的羟基空间关系的特定胆汁酸结构是诱导结肠ODC活性所必需的。
The changes of colonic epithelial ornithine decarboxylase (ODC) activity and DNA synthesis following intrarectal administration of a tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA), or various bile acids to male noninbred rats were studied. A single instillation of TPA, at a dose as low as 16 nmol, led to a significant (about 10-fold) increase in colonic ODC activity. Peak ODC activity was observed at 4 hr, and the enzyme activity returned to the control level about 24 hr after intrarectal TPA. This pattern was almost the same as that observed after sodium deoxycholate treatment. TPA showed more potent induction of ODC activity than deoxycholate, although the maximal induction was greater in the case of deoxycholate treatment. Both TPA and deoxycholate stimulated DNA synthesis at 2 days after intrarectal instillation, after an initial depression at 4-12 hr. A structure-activity study of 26 bile acids revealed that 5 beta-cholanoic acid with alpha-hydroxy groups in two of the 3 alpha, 7 alpha, 12 alpha positions and 5 beta-cholanoic acid with a 3 alpha-hydroxy group induced colonic ODC activity significantly, while the 3 alpha, 6 alpha-dihydroxy acid did not. Replacement of hydroxy groups by keto groups or a change from alpha to beta configuration decreased the ODC-inducing activities. Tri-substituted 5 beta-cholanoic acid derivatives, whether hydroxy or keto, did not stimulate ODC. These data indicate that a specific bile acid structure with a definite spatial relationship of the hydroxy groups is required for induction of colonic ODC activity.