Differential effects of 6-hydroxydopamine-induced ablation of peripheral and central adrenergic axons on C-1300 murine neuroblastoma tumor growth and catecholamine concentration in the A/J mouse

DW Fink, PT Horn and BL Mirkin

Children's Memorial Hospital, Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois.

The relationship between 6-hydroxydopamine (6-OHDA)-induced ablation of central and peripheral adrenergic neurons and in situ C-1300 murine neuroblastoma (MNB) tumor growth and catecholamine concentration were investigated. Destruction of central and/or peripheral adrenergic neurons was produced by the intracerebral and/or s.c. administration of 6-OHDA to neonatal A/J mice. Disaggregated MNB cells (1 x 10(6)) were implanted s.c. into each mouse 3 weeks after treatment with 6-OHDA or diluent. Tumor onset time (the time interval between implantation of MNB cells and detection of palpable tumor), tumor weight, tumor weight to body weight ratio, tumor growth rate constant and tissue catecholamine concentrations were determined. Central axotomy caused a significant increase in tumor onset time and decrease in tumor weight when compared to controls. However, neither the tumor weight to body weight ratio or tumor growth rate constant were significantly lowered. In contrast, a reduction in all tumor growth parameters was produced by peripheral axotomy, which differed significantly from centrally axotomized and control animals. The catecholamine concentration of MNB tumors excised from control and 6-OHDA-treated mice 8 days after tumor onset were determined. Norepinephrine and dopamine levels were elevated above controls in MNB tumors obtained from mice that had been either peripherally or peripherally and centrally axotomized; whereas, no change in tumor catecholamine concentrations was noted in centrally axotomized mice. This investigation has demonstrated that ablation of central as well as peripheral adrenergic innervation exerts an inhibitory effect on MNB tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 262, Issue 3, pp. 1070-1075, 09/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics