Poston G J, Saydjari R, Lawrence J P, Trudel J L, Rubin N H, Townsend C M, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Cancer Invest. 1993;11(4):400-7. doi: 10.3109/07357909309018872.
We measured the effect of MC-26 mouse colon cancers (of different sizes) on the circadian rhythm of hepatic ornithine decarboxylase (ODC) activity and hepatic ODC activity during the 24 hr after 60% hepatectomy. Tumor-free control mice showed a normal circadian rhythm of ODC activity with the highest levels at 1100 hr and the lowest levels at 2300 hr. The amplitude of the rhythm was diminished significantly in mice with a large tumor burden (3% of their body weight), and hepatic ODC activity was significantly less than in the tumor-free mice at every point during the 24 hr of the study. In mice with "early" tumors (0.3% of body weight), basal activity of ODC was normal and there was no reactive increase in activity following hepatectomy. In contrast, mice with "late" (3% of body weight) tumors had significantly lower basal ODC activities and the increase in ODC activity following hepatectomy was prolonged and exaggerated. We concluded that tumor burden is associated with abnormal ODC activity and that these differences are exaggerated after hepatectomy. Furthermore, although average ODC concentrations in tumor-bearing mice fell precipitously, the circadian rhythm in hepatic ODC persisted. This finding indicates early recognition by the host of tumor presence, which has a profound negative regulatory effect on hepatic ODC. Apparently, this effect does not impinge on circadian control mechanisms, indicating that these signals act independently.
我们测定了不同大小的MC - 26小鼠结肠癌对肝鸟氨酸脱羧酶（ODC）活性昼夜节律以及60%肝切除术后24小时内肝ODC活性的影响。无瘤对照小鼠表现出正常的ODC活性昼夜节律，在1100时活性最高，在2300时活性最低。在肿瘤负荷大（占体重3%）的小鼠中，节律幅度显著减小，并且在研究的24小时内的每个时间点，肝ODC活性均显著低于无瘤小鼠。在患有“早期”肿瘤（占体重0.3%）的小鼠中，ODC的基础活性正常，肝切除术后活性没有反应性增加。相反，患有“晚期”（占体重3%）肿瘤的小鼠基础ODC活性显著较低，肝切除术后ODC活性的增加延长且过度。我们得出结论，肿瘤负荷与ODC活性异常有关，并且这些差异在肝切除术后会加剧。此外，尽管荷瘤小鼠的平均ODC浓度急剧下降，但肝ODC的昼夜节律仍然存在。这一发现表明宿主对肿瘤存在的早期识别，这对肝ODC具有深远的负调节作用。显然，这种作用不会影响昼夜控制机制，表明这些信号是独立起作用的。
