Garewal H S, Gerner E W, Sampliner R E, Roe D
Section of Hematology-Oncology, Veterans Administration Medical Center, Tucson, Arizona 85723.
Cancer Res. 1988 Jun 1;48(11):3288-91.
Ornithine decarboxylase (ODC) activity was elevated in the premalignant metaplastic columnar epithelium (mean activity, 0.13 unit/mg protein, N = 18 individual samples from 18 patients), compared to either adjacent gastric (mean activity, 0.02 unit/mg protein, N = 9) or small intestinal (mean activity, 0.02 unit/mg protein, N = 9) epithelium in patients with Barrett's esophagus. Enzyme activity ranged from 0 (less than detectable) to more than 0.5 unit/mg protein in the metaplastic tissue. However, neither putrescine, spermidine, spermine (as individual parameters), nor total polyamine contents were related to ODC activity in the individual patient biopsies. Spermidine/spermine ratios ranged from 0.38 to 2.18 and were also not related to enzyme activity in any apparent manner. Nevertheless, cell strains derived from the metaplastic tissue were growth inhibited by alpha-difluoromethylornithine, an enzyme-activated, suicide inhibitor of ODC. In two different cell strains derived from Barrett's epithelium, growth was affected with drug concentrations as low as 0.05 mM. While the mechanism responsible for the elevation in enzyme activity is unknown, the regulation of polyamine metabolism appears to be altered in this premalignant tissue. The growth inhibition of Barrett's epithelium-derived cell lines by ODC inhibitors suggests a potential role for these compounds in the treatment of this disease.
与巴雷特食管患者的相邻胃上皮（平均活性为0.02单位/毫克蛋白，N = 9）或小肠上皮（平均活性为0.02单位/毫克蛋白，N = 9）相比，癌前化生柱状上皮中的鸟氨酸脱羧酶（ODC）活性升高（平均活性为0.13单位/毫克蛋白，N = 18个来自18例患者的个体样本）。化生组织中的酶活性范围为0（低于可检测水平）至超过0.5单位/毫克蛋白。然而，在个体患者活检中，腐胺、亚精胺、精胺（作为个体参数）以及总多胺含量均与ODC活性无关。亚精胺/精胺比值范围为0.38至2.18，也与酶活性无明显关联。尽管如此，源自化生组织的细胞系受到α-二氟甲基鸟氨酸的生长抑制，α-二氟甲基鸟氨酸是一种酶激活的ODC自杀抑制剂。在源自巴雷特上皮的两种不同细胞系中，低至0.05 mM的药物浓度即可影响生长。虽然酶活性升高的机制尚不清楚，但多胺代谢的调节在这种癌前组织中似乎发生了改变。ODC抑制剂对巴雷特上皮来源的细胞系的生长抑制表明这些化合物在该疾病治疗中具有潜在作用。
