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Angiogenesis determines blood flow, metabolism, growth rate, and ATPase kinetics of tumors growing in an irradiated bed: 31P and 2H nuclear magnetic resonance studies.
- Source :
-
Cancer research [Cancer Res] 1991 Jun 15; Vol. 51 (12), pp. 3289-95. - Publication Year :
- 1991
-
Abstract
- Experimental tumors growing in irradiated tissue have been used to study the biological differences characteristic of locally recurrent tumors. Since the hypoxic cell fraction of tumors growing in irradiated tissue is increased and growth rate is slowed, these tumors are assumed to be metabolically deprived with hypoperfusion. In this study, we directly measured the effect of tumor bed irradiation on blood flow, growth rate, rate of nucleoside triphosphate (NTP) turnover, and metabolic state using 31P and 2H nuclear magnetic resonance, and an intradermal assay for angiogenesis. (NTP turnover refers to ATP-synthetase mediated NTP turnover that is visible to 31P nuclear magnetic resonance using the technique of saturation transfer.) A decrease in the number of small blood vessels perfusing tumors in a preirradiated bed was found. Most of the decrease was due to a loss of vessels with diameters less than 0.04 mm. When tumors growing in preirradiated tissue reached approximately 100 mm3 in volume, a high frequency of gross and microscopic necrosis and hemorrhage was already observed in most tumors. Consistent with these observations, the phosphocreatine/inorganic phosphate and nucleoside triphosphate/inorganic phosphate ratios were significantly lower in the tumors growing in a preirradiated bed compared with tumors in a nonirradiated bed. The blood flow rate was similar to control for tumors less than 100 mm3 (45.8 versus 40.5 ml/100 g/min, P = not significant), but was significantly lower than control for tumors greater than 100 mm3 (40.4 versus 12.2 ml/100 g/min, P less than 0.01). The NTP turnover rates correlated (P less than 0.005, r = 0.66) with the volume doubling rate (1/tumor volume doubling time), but for tumors approximately 100 mm3 in size neither the volume doubling rate nor the NTP turnover rate of tumors growing in an irradiated bed was statistically lower than control [NTP turnover: 14 +/- 3%/s versus 9 +/- 2%/s; volume doubling rate: 0.47 +/- 0.07/day versus 0.33 +/- 0.04/day (mean +/- SE)]. A large intertumor variability of all metabolic parameters was observed.
- Subjects :
- Animals
Cell Division radiation effects
Deuterium
Fibrosarcoma blood supply
Fibrosarcoma enzymology
Fibrosarcoma pathology
Kinetics
Magnetic Resonance Spectroscopy methods
Mice
Mice, Inbred C3H
Mice, Nude
Phosphates metabolism
Phosphocreatine metabolism
Phosphorus
Regional Blood Flow radiation effects
Ribonucleotides metabolism
Sarcoma, Experimental blood supply
Sarcoma, Experimental enzymology
Sarcoma, Experimental pathology
Sarcoma, Experimental physiopathology
Adenosine Triphosphatases metabolism
Fibrosarcoma physiopathology
Muscles radiation effects
Neovascularization, Pathologic
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 51
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 1710169