These experiments were performed to determine the patterns of substrate utilization for energy production in tumors in vitro. A method is described for the growth of “tissue isolated” rat tumors. Implants of transplantable tumors are attached to a surgically prepared vascular pedicle composed of the superficial epigastric artery and vein. The vascular pedicle and tumor implant are enclosed in a parafilm envelope and placed in the inguinal fossa, and the skin incision is closed. Subsequent tumor growth is contained within the envelope, and vascularization of the tumor is entirely via the vascular pedicle. Tumors (1 to 6 g, wet weight) are harvested within 1 week to 2 months, depending on the growth rate. Blood samples may be collected by catheter from the tumor vein (superficial epigastric and femoral) and the carotid artery, or the tumor and pedicle may be removed and perfused. The overall success rate of the method, that is, tumor implants brought to successful blood sampling, is about 50%.
Arteriovenous differences for whole-blood amino acids, glucose, and lactic acid were measured in vitvo in Morris hepatomas 5123C, 7777, and 7288CTCF and Walker carcinosarcoma 256 grown by this method. Most whole-blood amino acids were utilized with mean utilization rates of 5 nmol/min/g tumor, wet weight, or less. Glutamine, the most abundant whole-blood amino acid, was also the most extensively utilized (mean utilization rates were 4 to 10 nmol/min/g). Ammonia was released into the venous blood by all tumors. The glucose utilization rate was directly proportional to the rate of glucose supply. Lactic acid was either produced or utilized, depending on the arterial blood lactic acid concentration. Lactate production occurred at arterial blood concentrations less than 2 to 3 mm, and utilization occurred at higher concentrations. The results show that new information on tumor-host organ inter-relationships and on the energy metabolism of tumors in vivo can be obtained using these techniques.
Supported by Grant CA 27809 from the USPHS, NIH, and the Stephen C. Clark Research Fund of the Mary Imogene Bassett Hospital.