Westin T, Gustafsson B, Hellander K, Reinholdtsen L, Tibell L, Lundholm K, Edström S
Department of Otolaryngology, Sahlgrenska Hospital, University of Gothenburg, Sweden.
Cytometry. 1991;12(7):628-35. doi: 10.1002/cyto.990120707.
Previous investigations in our laboratory have demonstrated that both acute host starvation and polyamine depletion by means of the irreversible ODC-inhibitor (ODC = ornithine-decarboxylase) fluoro-methylornithine (DFMO) lead to pronounced growth retardation of rapidly proliferating tumors. The aim of this investigation was to elucidate how these different interventions affect cell kinetics and cell cycle phases in vivo. Adult nongrowing mice (C57Bl/J) bearing a poorly differentiated rapidly growing methylcholanthrene induced sarcoma were used. Combined measurements of bromodeoxyuridine incorporation into DNA and flow cytometric techniques were used. Starvation and DFMO treatment resulted in a prolonged cell cycle transit compared to freely fed animals. Tumor cells from DFMO-treated mice demonstrated an increased time for DNA synthesis and a relatively larger accumulation of cells in the G2M phase, whereas tumor cells from starved animals were accumulated in the G0G1 phase. The fractional cell loss of tumor cell during proliferation was calculated to be around 18% higher in DFMO-treated animals compared to starved and freely fed tumor-bearing mice. This study demonstrates that different mechanisms are involved in tumor growth suppression from substrate deficiency (starvation) and from inhibition of polyamine synthesis.
我们实验室之前的研究表明，急性宿主饥饿以及通过不可逆的鸟氨酸脱羧酶（ODC）抑制剂氟甲基鸟氨酸（DFMO）消耗多胺，都会导致快速增殖肿瘤的显著生长迟缓。本研究的目的是阐明这些不同的干预措施如何在体内影响细胞动力学和细胞周期阶段。使用成年非生长状态的C57Bl/J小鼠，其携带一种低分化的快速生长的甲基胆蒽诱导肉瘤。采用将溴脱氧尿苷掺入DNA的联合测量方法和流式细胞术技术。与自由进食的动物相比，饥饿和DFMO处理导致细胞周期进程延长。来自DFMO处理小鼠的肿瘤细胞显示DNA合成时间增加，并且在G2M期细胞积累相对更多，而来自饥饿动物的肿瘤细胞则积累在G0G1期。与饥饿和自由进食的荷瘤小鼠相比，DFMO处理动物的肿瘤细胞在增殖过程中的细胞分数损失计算得出高约18%。这项研究表明，底物缺乏（饥饿）和多胺合成抑制在肿瘤生长抑制中涉及不同的机制。
