Proietti E, Carpinelli G, Di Vito M, Belardelli F, Gresser I, Podo F
Cancer Res. 1986 Jun;46(6):2849-57.
Adult DBA/2 mice were given injections s.c. with either interferon-sensitive (745) or -resistant (3Cl-8) Friend erythroleukemia cells (FLC). After tumor nodules had developed, mouse interferon-alpha/beta was injected daily into the tumor. 31P-Nuclear magnetic resonance (NMR) spectroscopy examinations were undertaken on freshly dissected tumors at different days of treatment with either interferon or control preparations. Analysis of 745 FLC tumors in untreated mice at different days of tumor growth (day 8 to 13 after tumor implantation) showed marked increases in the levels of phosphorylcholine (PCho), glycerophosphorylethanolamine (GroPEtn) and glycerophosphorylcholine (GroPCho). In contrast high levels of PCho, GroPEtn and GroPCho were already detectable in the 3Cl-8 FLC tumors on day 8, and no significant changes were observed during subsequent tumor growth. The intracellular pH value remained practically constant in both FLC tumors. Daily intratumoral administration of either partially purified (10(7) IU/mg of protein) or highly purified (10(9) IU/mg of protein) mouse interferon-alpha/beta to both cell tumors resulted in decreases in the levels of PCho, GroPEtn and GroPCho and in increases in the intracellular pH with respect to tumors treated with control preparations or left untreated. Two days of daily treatment of mice with interferon sufficed to induce these metabolic changes which preceded the appearance of necrosis in the tumors. Treatment of FLC tumors with X-rays on day 12 of tumor growth did not result in any comparable metabolic changes 2 days after irradiation. Changes in the levels of phospholipid metabolites were not observed when 745 or 3Cl-8 cells were cultivated in the presence of interferon. As interferon induced these changes in both interferon-sensitive and -resistant tumors we conclude that interferon treatment results in host-mediated effects on the biosynthesis and/or catabolism of tumor cell phospholipids.
将成年DBA/2小鼠皮下注射干扰素敏感型（745）或耐药型（3Cl-8）弗氏白血病细胞（FLC）。肿瘤结节形成后，每天向肿瘤内注射小鼠α/β干扰素。在用干扰素或对照制剂治疗的不同天数，对新鲜解剖的肿瘤进行31P-核磁共振（NMR）光谱检查。对未治疗小鼠在肿瘤生长不同天数（肿瘤植入后第8至13天）的745 FLC肿瘤分析显示，磷酸胆碱（PCho）、甘油磷酸乙醇胺（GroPEtn）和甘油磷酸胆碱（GroPCho）水平显著升高。相比之下，在第8天3Cl-8 FLC肿瘤中已可检测到高水平的PCho、GroPEtn和GroPCho，在随后的肿瘤生长过程中未观察到显著变化。两种FLC肿瘤中的细胞内pH值基本保持恒定。对两种细胞肿瘤每天瘤内注射部分纯化（10^7 IU/mg蛋白质）或高度纯化（10^9 IU/mg蛋白质）的小鼠α/β干扰素，与用对照制剂治疗或未治疗的肿瘤相比，PCho、GroPEtn和GroPCho水平降低，细胞内pH值升高。用干扰素对小鼠进行两天的每日治疗足以诱导这些代谢变化，这些变化先于肿瘤中坏死的出现。在肿瘤生长第12天用X射线治疗FLC肿瘤，照射后2天未导致任何类似的代谢变化。当745或3Cl-8细胞在干扰素存在下培养时，未观察到磷脂代谢物水平的变化。由于干扰素在干扰素敏感型和耐药型肿瘤中均诱导了这些变化，我们得出结论，干扰素治疗导致宿主介导的对肿瘤细胞磷脂生物合成和/或分解代谢的影响。
