Boyle J O, Meyskens F L, Garewal H S, Gerner E W
University of Arizona, Arizona Cancer Center, Tucson.
Cancer Epidemiol Biomarkers Prev. 1992 Jan-Feb;1(2):131-5.
Difluoromethylornithine (DFMO) is an investigational chemopreventive agent that inhibits ornithine decarboxylase (ODC) activity, lowers cellular polyamine concentrations, and decreases cell proliferation in vivo and in vitro. In five subjects we have compared the polyamine concentrations in rectal mucosal biopsies and in exfoliated buccal mucosal cells (EBM) before and after DFMO treatment to assess the suitability of EBM as an easily accessible marker tissue for DFMO suppression of polyamine synthesis in the rectal mucosa. One month of 3 g/m2/day of DFMO treatment caused a statistically significant decrease in putrescine and spermidine concentrations in rectal mucosa biopsy specimens but not in EBM samples. ODC activity in EBM was high (approximately 1 mumol/min/mg protein), resistant to DFMO inhibition (Ki = 4200 microM), dependent on GTP concentration (maximal at 0.1 mM), and was reduced concomitantly with bacterial concentration by antiseptic mouthwashing. Bacteria adherent to EBM were visible by electron microscopy. Forty bacterial colonies/ng protein were culturable from washed EBM samples. Oral bacteria preclude the use of EBM samples as a marker tissue of DFMO effect in the rectal mucosa, but oral DFMO therapy is effective in depleting polyamines in rectal mucosa.
二氟甲基鸟氨酸（DFMO）是一种正在研究的化学预防剂，它能抑制鸟氨酸脱羧酶（ODC）的活性，降低细胞内多胺浓度，并在体内和体外降低细胞增殖。我们对5名受试者在DFMO治疗前后直肠黏膜活检组织和颊黏膜脱落细胞（EBM）中的多胺浓度进行了比较，以评估EBM作为一种易于获取的标记组织，用于检测DFMO对直肠黏膜多胺合成抑制作用的适用性。每天3 g/m²的DFMO治疗1个月后，直肠黏膜活检标本中的腐胺和亚精胺浓度出现了统计学上的显著下降，但EBM样本中的浓度未下降。EBM中的ODC活性较高（约1 μmol/min/mg蛋白质），对DFMO抑制具有抗性（Ki = 4200 μM），依赖于GTP浓度（在0.1 mM时达到最大值），并且通过抗菌漱口水可使其活性随细菌浓度的降低而降低。通过电子显微镜可观察到附着在EBM上的细菌。从洗涤后的EBM样本中每纳克蛋白质可培养出40个细菌菌落。口腔细菌妨碍了将EBM样本用作直肠黏膜中DFMO效应的标记组织，但口服DFMO疗法可有效降低直肠黏膜中的多胺含量。
