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Division of Clinical Pharmacology, Departments of Pediatrics and Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455
The C-1300 murine neuroblastoma has been biologically and biochemically characterized to determine its suitability as an in vivo neural crest tumor model for pharmacological studies. The tumor line was sustained in vivo by s.c. implantation of tissue segments or disaggregated tumor cells (106/inoculum) into recipient A/J mice. Palpable tumors were initially detected 8.1 ± 1.1 (S.E.) days after inoculation (n = 69). Daily tumor growth (estimated by transverse diameter) followed a Gompertzian-like growth curve. The survival time of implanted animals was 18.2 ± 1.0 days after initial detection. Metastatic involvement of specific organs occurred with the following frequency: liver, 83%; kidney, 42%; and spleen, 29%.
Biological specimens from control and tumor-implanted animals were assayed for catecholamines using high-pressure liquid chromatography coupled to an electrochemical detector. Dopamine and norepinephrine were present in the primary tumors, whereas no epinephrine was detected. In contrast, metastases obtained from the liver contained large concentrations of dopamine, norepinephrine, and epinephrine. The serum concentrations of dopamine and norepinephrine in tumorbearing mice and the 24-hr urinary secretion of dopamine and norepinephrine were significantly greater than in non-tumorbearing animals.
This investigation has shown the in vivo C-1300 murine neuroblastoma to be a highly reproducible tumor model that is lethal, exhibits constant growth patterns, metastasizes, and secretes catecholamines. It should be useful to analyze the effects of chemotherapeutic agents upon in vivo tumor growth and to clarify their biochemical mechanisms of action.
1 Investigation partially supported by USPHS Grants NS-17194 and GM-07466 and the Minnesota Medical Foundation. A preliminary report of this work was presented at the 65th Annual meeting of the Federation of American Society for Experimental Biology, Atlanta, Ga. (23).
2 Recipient of a Postdoctoral Fellowship in Clinical Pharmacology from des Ministere des Affaires Etrangères (France) and the Delegation Generale a la Recherche Scientifique et Technique (D. G. R. S. T., France).
3 Research Career Developmental awardee of the National Heart, Lung, and Blood Institute, USPHS-(HL-00565).
4 To whom requests for reprints should be addressed, at Division of Clinical Pharmacology, Box 87, Mayo, University of Minnesota Medical School, Minneapolis, Minn. 55455.
Received 12/28/81. Accepted 6/15/82.
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