Fink D W, Mirkin B L
NIGMS/NICHD, National Institutes of Health, Bethesda, Maryland.
J Neurosci Res. 1991 Mar;28(3):343-51. doi: 10.1002/jnr.490280305.
The in situ C-1300 murine neuroblastoma (MNB) tumor model was used to investigate the influence of exogenously administered nerve growth factor (NGF) on tumor growth and tissue catecholamine concentration in mice sympathectomized with 6-hydroxy-dopamine (6-OHDA) on postnatal days 4-10. Mice were implanted with 1 x 10(6) disaggregated MNB cells 3 days after termination of 6-OHDA administration. NGF (12-15 micrograms/mouse/day) treatment was initiated at the time of MNB cell implantation and continued until sacrifice of the animal. The time interval between tumor cell implantation 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. Neonatal sympathectomy caused a decrease in myocardial norepinephrine concentration of 88% compared with vehicle-treated animals as well as a significant reduction in total body and organ weight. Average body, brain, heart, and spleen weights were decreased 31%, 16%, 25%, and 42%, respectively, below control values. The daily injection of NGF, from the time of MNB tumor implantation to sacrifice, did not prevent these effects of chemical sympathectomy from being expressed. Tumor onset time following implantation of MNB cells was significantly increased in neonatally sympathectomized mice and was not altered by treatment with NGF. In contrast, the decrease in MNB tumor growth rate observed in sympathectomized mice was reversed by administration of NGF. Mean tumor weight and mean tumor to body weight ratio were 89% and 115% of comparable control values, respectively, in sympathectomized mice receiving exogenous NGF.(ABSTRACT TRUNCATED AT 250 WORDS)
采用原位C-1300小鼠神经母细胞瘤(MNB)肿瘤模型,研究外源性给予神经生长因子(NGF)对出生后第4至10天用6-羟基多巴胺(6-OHDA)进行交感神经切除术的小鼠肿瘤生长及组织儿茶酚胺浓度的影响。在6-OHDA给药结束后3天,给小鼠植入1×10⁶个分散的MNB细胞。在植入MNB细胞时开始NGF(12 - 15微克/小鼠/天)治疗,并持续至动物处死。测定肿瘤细胞植入与可触及肿瘤检测之间的时间间隔(肿瘤起始时间)、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。与给予赋形剂处理的动物相比,新生期交感神经切除术使心肌去甲肾上腺素浓度降低了88%,同时全身和器官重量也显著降低。平均体重、脑重、心脏重量和脾脏重量分别比对照值降低了31%、16%、25%和42%。从MNB肿瘤植入到处死期间每日注射NGF,并不能阻止化学交感神经切除术的这些效应的显现。新生期交感神经切除的小鼠在植入MNB细胞后的肿瘤起始时间显著延长,且NGF治疗未改变这一情况。相反,给予NGF可逆转交感神经切除小鼠中观察到的MNB肿瘤生长速率的降低。在接受外源性NGF的交感神经切除小鼠中,平均肿瘤重量和平均肿瘤与体重之比分别为相应对照值的89%和115%。(摘要截选至250字)