Fink D W, Mirkin B L
Department of Pediatrics, University of Minnesota Health Sciences Center, Minneapolis 55455.
Cancer Res. 1987 Nov 1;47(21):5620-5.
The in situ C-1300 murine neuroblastoma (MNB) tumor model was used to investigate the influence of 6-hydroxydopamine (6HD)-induced sympathectomy on tumor growth and catecholamine concentration. One week (adult) and 3 weeks (neonatal) after sympathectomy, mice were implanted with 10(6) disaggregated MNB cells. The time interval between implantation of MNB cells and detection of palpable tumor (tumor onset time), transverse tumor diameter, tumor weight, tumor weight to body weight ratio, and tumor catecholamine concentration were determined. Sympathectomy following 6HD administration was confirmed by analysis of catecholamine concentrations in the heart and spleen by high-pressure liquid chromatography. Treatment of adult animals with 6HD reduced the mean heart and spleen norepinephrine (NE) concentrations to less than 20% of controls (vehicle treated). Neonatal sympathectomy decreased the average heart and spleen NE concentrations to less than 10% of comparable control mice. Whole brain NE and dopamine concentrations were not altered by treatment with 6HD in either age group. Tumor onset time following implantation of MNB cells was significantly increased in animals sympathectomized as either neonates or as adults. In contrast, MNB tumor growth rate following tumor onset was significantly inhibited in animals sympathectomized as neonates but not as adults. The catecholamine concentrations of tumors removed from control and sympathectomized mice 8 days after tumor onset were determined. Tumor NE and dopamine concentrations were increased 9.09 +/- 2.8- (SE) and 7.03 +/- 1.8-fold, respectively, in mice sympathectomized as neonates. There were no significant differences in the NE and dopamine concentrations of tumors obtained from sympathectomized and control adult mice. Pretreatment with desmethylimipramine prior to 6HD administration prevented destruction of sympathetic neurons, inhibition of tumor growth rate, and the increase in tumor catecholamine concentration observed in neonatally sympathectomized mice. These data suggest that the influence of chemical sympathectomy on MNB tumor growth and biochemical differentiation, as defined by catecholamine content, are age dependent.
采用原位C - 1300小鼠神经母细胞瘤（MNB）肿瘤模型，研究6 - 羟基多巴胺（6HD）诱导的交感神经切除术对肿瘤生长和儿茶酚胺浓度的影响。交感神经切除术后1周（成年）和3周（新生），给小鼠植入10⁶个分散的MNB细胞。测定MNB细胞植入与可触及肿瘤检测之间的时间间隔（肿瘤发病时间）、肿瘤横向直径、肿瘤重量、肿瘤重量与体重之比以及肿瘤儿茶酚胺浓度。通过高压液相色谱分析心脏和脾脏中的儿茶酚胺浓度，证实6HD给药后交感神经切除术成功。用6HD处理成年动物可使心脏和脾脏去甲肾上腺素（NE）的平均浓度降至对照组（用赋形剂处理）的20%以下。新生期交感神经切除术使心脏和脾脏NE的平均浓度降至可比对照小鼠的10%以下。两个年龄组用6HD处理均未改变全脑NE和多巴胺浓度。新生期或成年期进行交感神经切除术的动物，植入MNB细胞后的肿瘤发病时间均显著延长。相比之下，新生期进行交感神经切除术的动物肿瘤发病后的MNB肿瘤生长速率显著受到抑制，成年期进行交感神经切除术的动物则未受抑制。测定肿瘤发病8天后从对照和交感神经切除小鼠身上切除的肿瘤的儿茶酚胺浓度。新生期进行交感神经切除术的小鼠肿瘤NE和多巴胺浓度分别增加了9.09±2.8（SE）倍和7.03±1.8倍。从交感神经切除和对照成年小鼠获得的肿瘤的NE和多巴胺浓度没有显著差异。在6HD给药前用去甲丙咪嗪预处理可防止新生期进行交感神经切除术的小鼠中观察到的交感神经元破坏、肿瘤生长速率抑制以及肿瘤儿茶酚胺浓度增加。这些数据表明，化学交感神经切除术对MNB肿瘤生长和生化分化（以儿茶酚胺含量定义）的影响具有年龄依赖性。
