Effect of nerve growth factor on C-1300 murine neuroblastoma tumor growth and catecholamine content in neonatally sympathectomized mice.
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)
Fink
D W
DW
NIGMS/NICHD, National Institutes of Health, Bethesda, Maryland.
Mirkin
B L
BL
D000818:Animals; D000831:Animals, Newborn; D006892:Hydroxydopamines / Q000633:toxicity; D051379:Mice; D008805:Mice, Inbred A; D009206:Myocardium / Q000737:chemistry; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology*; D009638:Norepinephrine / Q000032:analysis; D016627:Oxidopamine; D013563:Sympathectomy, Chemical
D006892:Hydroxydopamines; D009414:Nerve Growth Factors; D016627:Oxidopamine; D009638:Norepinephrine