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Intracellular acidosis in murine fibrosarcomas coincides with ATP depletion, hypoxia, and high levels of lactate and total P i
Author(s) -
Vaupel P.,
Schaefer C.,
Okunieff P.
Publication year - 1994
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.1940070305
Subject(s) - intracellular ph , energy charge , phosphocreatine , adenylate kinase , intracellular , bioenergetics , acidosis , medicine , lactic acidosis , lactic acid , chemistry , endocrinology , glycolysis , hypoxia (environmental) , metabolism , biology , oxygen , biochemistry , energy metabolism , enzyme , mitochondrion , genetics , bacteria , organic chemistry
Bioenergetic and metabolic status of murine FSaII tumours were evaluated using 31 P MRS, acid extracts (‘global’ techniques) and quantitative bioluminescence (‘microregional’ assay). Data obtained from s.c. tumours of varying sizes (44–600 mm 3 ) have been correlated with the oxygenation status evaluated using O 2 ‐sensitive needle electrodes. β‐NTP/P i and phosphocreatine (PCr)/P i ratios derived from 31 P MRS were positively correlated to the median tissue p O 2 values. pH declined during growth with intracellular acidosis being evident in tumours >350 mm 3 . Whereas lactic acid formation greatly contributed to this decline in small‐ and medium‐sized tumours, ATP hydrolysis and slowing down of the activities of pumps involved in pH i regulation seem to be major factors responsible for intracellular acidification in bulky tumours. PCr levels decreased at an early growth stage, whilst ATP concentrations dropped in bulky malignancies only, coinciding with a decrease in adenylate energy charge and a substantial rise in the levels of total P i . MRS observable (mobile) P i was consistently lower than [P i ] measured in acid extracts. On average, median p O 2 values of ca 10 mmHg represent a critical threshold for energy metabolism. At higher median O 2 tensions, levels of ATP, phosphomonoester and total P i were relatively constant. This coincided with intracellular alkalosis or neutrality and stable adenylate ratios. On average, median p O 2 values < 10 mmHg coincided with intracellular acidosis, ATP depletion, a drop in energy charge and rising P i levels.