BLOOD-FLOW, OXYGENATION, METABOLIC AND ENERGETIC STATUS IN DIFFERENT CLONAL SUBPOPULATIONS OF A RAT RHABDOMYOSARCOMA

Differentiation of a tumor plays an important role in terms of biologi cal aggressiveness. The question arises as to whether this is reflecte d in differences in the metabolic and energetic status of solid tumors . The aim of this study was to analyze the influence of clonal tumor c ell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-I) with different his tomorphological properties were used (line F1, co-existence of mononuc lear stellate cells and multinuclear myotube-like giant tumor cells; G 8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. o n the hind food dorsum of Lewis rats. Tumor oxygenation was measured u sing O-2-sensitive needle electrodes. For determining tumor blood flow , the Xe-133 clearance method was used. Global glucose and lactate con centrations were measured enzymatically, global ATP, ADP, and AMP were analyzed by HPLC. The regional distribution of metabolic and energeti c parameters within the tumors was analyzed using quantitative biolumi nescence and image analysis. Tumor growth rate was significantly diffe rent between the two lines. The volume doubling time was 2.5 days for the Fl and 3.0 days for G8 tumors. No differences in blood flow were s een between the two lines investigated, oxygenation was slightly poore r, glucose and ATP levels slightly higher, and lactate concentration s omewhat lower in the Fl line as compared to the G8 line. From these di fferences - although marginal - it is concluded that the G8 line presu mably relies on glycolysis whereas the Fl line seems to prefer oxidati ve glucose turnover. Despite these different metabolic profiles betwee n the two tumor lines, the histopathology of the rhabdomyosarcomas see ms to be only of limited significance for the tissue oxygenation statu s as already postulated for various tumors in the clinical setting.