Takano S, Matsushima M, Ertürk E, Bryan G T
Cancer Res. 1981 Feb;41(2):624-8.
The responses of male noninbred rat colonic epithelial ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) (SAMD) activities following topical administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or bile salts were studied. A single intrarectal installation of 13 mumol of MNNG resulted in a significant (p < 0.001) 20-fold peak ODC activity after 4 hr, with a prompt return to control levels by 12 hr. Stimulation of SAMD activity was less pronounced but significant (p < 0.01), with a broad 2-fold peak over controls. No significant responses of colonic epithelial enzyme activities were detected following a single intrarectal instillation of N-methyl-N'-nitroguanidine, a noncarcinogenic and nonmutagenic metabolite of MNNG, at a dose equimolar to that of MNNG. Bile salts significantly (p < 0.001) induced ODC with almost the same kinetic pattern as that observed after MNNG administration in the following order: sodium deoxycholate > sodium chenodeoxycholate > sodium cholate. Activations of SAMD were similar for these 3 bile salts. Glycine- or taurine-conjugated deoxycholate showed ODC and SAMD enzyme activations similar to that of nonconjugated deoxycholate. No significant enzyme response was seen after sodium dehydrocholate treatment. Stimulation of activities of both enzymes was directly dependent on bile salt dose. Induced ODC and SAMD activities were principally localized in colonic epithelium. Deoxycholate-stimulated enzyme activities were significantly inhibited by cycloheximide. Enzyme stimulations by active compounds were accompanied by morphological changes such as mucosal cell degeneration, mucus depletion, submucosal congestion, and punctate hemorrhage, followed by submucosal leukocytic cellular infiltration. These data support the concept that initiating and promoting events may be involved in colon carcinogenesis.
研究了雄性非近交系大鼠结肠上皮鸟氨酸脱羧酶（EC 4.1.1.17）（ODC）和S-腺苷-L-甲硫氨酸脱羧酶（EC 4.1.1.50）（SAMD）在局部应用N-甲基-N'-硝基-N-亚硝基胍（MNNG）或胆盐后的活性变化。直肠内单次注入13 μmol的MNNG后，4小时时ODC活性显著升高（p < 0.001），达到峰值时比对照组高20倍，12小时时迅速恢复到对照水平。SAMD活性的刺激作用虽不那么明显，但也具有显著性（p < 0.01），比对照组有一个宽泛的2倍峰值。在直肠内单次注入与MNNG等摩尔剂量的N-甲基-N'-硝基胍（MNNG的一种非致癌和非诱变代谢产物）后，未检测到结肠上皮酶活性有显著变化。胆盐显著（p < 0.001）诱导ODC，其动力学模式与MNNG给药后观察到的模式几乎相同，顺序如下：脱氧胆酸钠>鹅脱氧胆酸钠>胆酸钠。这三种胆盐对SAMD的激活作用相似。甘氨酸或牛磺酸结合的脱氧胆酸盐对ODC和SAMD的酶激活作用与未结合的脱氧胆酸盐相似。脱氢胆酸钠处理后未观察到明显的酶反应。两种酶活性的刺激直接依赖于胆盐剂量。诱导的ODC和SAMD活性主要定位于结肠上皮。脱氧胆酸盐刺激的酶活性被环己酰亚胺显著抑制。活性化合物对酶的刺激伴随着形态学变化，如黏膜细胞变性、黏液消耗、黏膜下充血和点状出血，随后是黏膜下白细胞浸润。这些数据支持了启动和促进事件可能参与结肠癌发生的概念。
