Phosphomonoesters Research Articles

Phosphorus-31 metabolism of post-menopausal breast cancer studied in vivo by magnetic resonance spectroscopy

We have studied the metabolism of 31P-containing metabolites of post-menopausal breast cancers in vivo using magnetic resonance spectroscopy (MRS) and a 5.5 cm surface coil. Spectra were acquired from 23 diameter. The spectra of the 19 previously untreated tumours had significantly higher phosphomonoester (PME) 31P relative peak areas than the normal breasts of eight post-menopausal women (11.7% and 7.7% respectively, P = 0.002). Although an increased PME relative peak area was characteristic of malignancy, PME relative peak area is similarly raised in lactating breast and, therefore, not a specific feature of cancer. An apparently lower nucleotide triphosphate (NTP) relative peak area in tumours than healthy postmenopausal breast was secondary to the differences in PME relative peak area; contamination by signal from chest wall muscle probably accounts for the ostensibly higher phosphocreatine (PCr) relative peak area of the tumours. Spectroscopy was repeated following chemotherapy in six women. An increase in PCr relative peak area was seen in all five patients who responded, but again this may represent increased contamination secondary to changes in tumour size. A fall in PME relative peak area was noted in four responders, but also one non-responder, so this finding may not be sufficiently specific to be of use clinically. Further studies are need to elucidate fully the role of MRS in breast cancer.

In vivo and in vitro 31P magnetic resonance spectroscopic studies of the hepatic response of healthy rats and rats with acute hepatic damage to fructose loading.

The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.

Phosphorus metabolism during growth of lymphoma in mouse liver: a comparison of 31P magnetic resonance spectroscopy in vivo and in vitro

Large phosphomonoester (PME) signals are detected in the phosphorus magnetic resonance spectra (31P MRS) of many neoplastic and rapidly dividing tissues. In addition, alterations in phosphodiester (PDE) signals are sometimes seen. The present study of a murine lymphoma growing in liver showed a positive correlation between the hepatic PME/PDE ratio measured in vivo by 31P MRS at 4.7 T and the degree of lymphomatous infiltration in the liver, quantified by histology. High-resolution 31P MRS of liver extracts at 9.7 T showed that the PME peak consists largely of phosphoethanolamine (PE) and to a lesser extent of phosphocholine (PC). The concentration of both PE and PC increased positively with lymphomatous infiltration of the liver. In vivo, the PDE peak contains signals from phospholipids (mostly phosphatidylethanolamine and phosphatidylcholine) and the phospholipid breakdown products glycerophosphoethanolamine (GPE) and glycerophosphocholine (GPC). Low levels of GPE and GPC were detected in the aqueous extracts of the control and infiltrated livers; their concentrations remained unchanged as the infiltration increased. The total concentration of phospholipids measured by 31P MRS of organic extracts decreased about 3-fold as the infiltration increased to 70%. Thus, our data showed that the increased PME/PDE ratio in vivo is due to both an increase in the PME metabolites and a decrease in the PDE metabolites. We propose that this ratio can be used as a non-invasive measure of the degree of lymphomatous infiltration in vivo.

Phosphorus-31 magnetic resonance spectroscopy and ventricular enlargement in bipolar disorder

Phosphorus-31 magnetic resonance spectroscopy ( 31P-MRS) was used to examine whether reduced levels of phosphomonoesters (PME) were correlated with ventricular enlargement in 40 patients with bipolar disorder and 60 agematched normal control subjects. Ventricular enlargement was assessed by magnetic resonance imaging ( 1H-MRI) using the following three methods: Evans ratio (ER), Huckman number (HN), and minimum distance of caudate nuclei (MDCN). Although MDCN and ER were significantly larger in the patient group, no significant correlations were found between 31P-MRS and 1H-MRI. PME was negatively correlated with age in bipolar disorder. Decreased levels of PME were found only in bipolar I disorder. Intracellular pH was positively correlated with duration of lithium treatment. These results suggest that the observed PME reduction was not related to ventricular enlargement, but the issue should be further studied with volumetric MRI analysis.

Hepatic metabolism during constant infusion of fructose; comparative studies with 31P-magnetic resonance spectroscopy in man and rats

A protocol of constant infusion of fructose has been carried out both in human volunteers and in the perfused rat liver, aiming at a steady-state blood fructose concentration of 6–8 mM. Localized 31P-NMR spectroscopy and biochemical analyses were used to evaluate the metabolic changes. Comparison of the model experiment and the clinical study allowed an evaluation of this protocol as a clinically relevant assessment of the metabolic function of the liver. The time course of change, as well as the quasi steady-state levels reached during fructose infusion, for phosphomonoesters (PME), ATP and inorganic phosphate (P i) provided the following results: During fructose infusion, ATP and P i reached a steady-state level of 74.0 ± 5.9 and 54.6 ± 3.3% of control respectively, in the human volunteers. The corresponding data in the rat liver was 71.3 ± 4.3 and 54.4 ± 4.3%. Hepatic clearance of fructose was 0.53 and 0.52 ml · gl liver −1 · min −1 for volunteers and rats, respectively. The time course of intracellular metabolite recovery after fructose could be approximated by a first order kinetic. The rate constants for PME and ATP change were similar during fructose infusion and recovery, while after the discontinuation of fructose infusion P i increased with a rate constant significantly greater than during its fructose-induced depletion in human liver ( P < 0.005). Thus, this relatively simple clinically applicable protocol seems to be verifiable in the well controlled perfused rat liver model, and it is argued that it may be useful in the clinical evaluation of the metabolic functional capacity of the human liver.

Fructose 3-phosphate and 5-phosphoribosyl-1-pyrophosphate formation in perfused human erythrocytes: 31P NMR studies.

31P NMR was used to study the formation of fructose 3-phosphate (F3P) and 5-phosphoribosyl-1-pyrophosphate (PRPP) in perfused human erythrocytes, in the presence of 10 different combinations and concentrations of glucose, inosine, pyruvate, fructose, and inorganic phosphate (Pi). (1) The cells were immobilized in alginate-coated agarose threads and perfused with a medium containing fructose, and the level of F3P increased continuously over more than 10 h. The net rate of F3P formation was independent of the concentration of 2,3-bisphosphoglycerate (2,3-DPG) present in the cells. (2) PRPP was formed in high concentrations, relative to normal, in immobilized cells when they were perfused with a medium containing Pi at a low pH (6.6). (3) The 2,3-DPG level decreased simultaneously when the sample was perfused with a medium containing fructose, but without inosine or pyruvate. The measured intracellular pH and free Mg2+ concentration were constant in these experiments. (4) The experiments confirmed the presence of fructose-3-phosphokinase (E.C. 2.7.1.-) and ribose-phosphate pyrophosphokinase (E.C. 2.7.6.1) activity in the human erythrocytes and that the biosynthetic pathways are active in immobilized cells at 37 degrees C. (5) The rates of accumulation of 2,3-DPG and phosphomonoesters (PME) appeared to be strongly correlated.

Magnetic resonance spectroscopy of naso-sinus tumors

Magnetic Resonance Spectroscopy (MRS) has been developed as a new application of nuclear magnetic resonance. By means of MRS, internal chemical information can be non-invasively measured. In this study, the 31P MRS of naso-sinus tumors was measured and evaluated. The peaks of 31P MRS, such as Adenosine tri-phosphate (ATP), Creatine phosphate (PCr), Phosphodiester (PME), Inorganic phosphate (Pi), and Phosphomonoester (PME) can be identified. Phosphomonoesters (PME) are precursors of membrane phospholipids. Phosphodiesters (PDE) are metabolites of phospholipids. Compared with benign tumors, the 31P MRS of malignant tumors shows a higher PME peak and lower PDE and PCr peaks. These results indicate that malignant tumors are characterized by chemical changes in membrane metabolism.

Phosphorus-31 nuclear magnetic resonancein Vivo spectroscopy of human liver during hepatitis a virus infection

To evaluate the changes in hepatocellular phospholipid metabolism during hepatitis virus infection, 26 patients with acute viral hepatitis A were studied by means of phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. The spectroscopy of liver showed six signal components in all patients as well as in the normal volunteers. During the early phase of illness, the phosphomonoester (PME)-phosphodiester (PDE) ratios in the patients became markedly greater than the ratios in the controls (P < 0.001). Within six weeks after the onset, the PME/PDE ratios returned to the level of controls. The time course analysis indicated an inverse correlation between the PME/PDE ratio and the period of time after onset (r = 0.738, P < 0.001). The spectral changes of human liver observed in acute viral hepatitis A are similar to those in the regenerating rat liver, indicating that 31P-NMR spectroscopy allows a noninvasive study of cell turnover in human liver disease associated with acute virus infection.

Phosphorus-31 metabolism of human breast—an in vivo magnetic resonance spectroscopic study at 1.5 Tesla

We have studied the metabolism of compounds containing 31P in normal breast using magnetic resonance spectroscopy (MRS). Spectra were acquired from non-lactating pre-menopausal breast (n = 14 women), lactating breast (n = 8) and post-menopausal breast (n = 8). The standard acquisition protocol used a 5.5 cm surface coil with the volunteer prone to minimize chest wall signal contamination. In pre-menopausal non-lactating women the phosphocreatine (PCr) peak area, expressed relative to the sum of all 31P peak areas, was negatively correlated with breast size (r = -0.56, p = 0.02) suggesting that much of the PCr signal originated from the chest wall. The phosphodiester (PDE) relative peak area was positively correlated with breast size (r = 0.71; p = 0.002). Spectra could be acquired at all phases of the menstrual cycle. In sequential examinations of five women not taking the oral contraceptive pill (OCP), phosphomonoester (PME) relative peak area was significantly lower on Week 2 than other weeks of the cycle (p = 0.03). Among pre-menopausal women no clear difference was apparent between the spectra from women taking the OCP and those not taking the OCP. Lactating breast had significantly higher PME relative peak area than non-lactating pre-menopausal breast (p = 0.02), probably reflecting the higher proportion of epithelial tissue in lactation; the lower PCr relative peak area in lactating breast (p = 0.05) is probably due to the greater size of the breast during lactation. Spectra were acquired from post-menopausal women but with a relatively low signal-to-noise ratio. The only significant difference between 31P relative peak areas of breast spectra acquired from pre- and post-menopausal women was that less PCr was detected in the post-menopausal volunteers (p = 0.03), probably as a result of differences in breast size.

31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma xenograft lines: tumour bioenergetic status and blood supply.

Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to search for possible relationships between 31P-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The latter parameter was measured by using the 86Rb uptake method. Tumour bioenergetic status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per viable tumour cell decreased with increasing tumour volume for five of the six xenograft lines. The decrease in tumour bioenergetic status was due to a decrease in the (PCr + NTP beta)/total resonance ratio as well as an increase in the Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTP beta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTP beta)/total resonance ratio and the magnitude of the decrease in tumour pH were correlated to the magnitude of the decrease in blood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was larger for the tumour lines showing a high than for those showing a low blood supply per viable tumour cell. No correlations across the tumour lines were found between tumour pH and tumour bioenergetic status or any other resonance ratio on the one hand and blood supply per viable tumour cell on the other. The differences in the 31P-NMR spectrum between the tumour lines were probably caused by differences in the intrinsic biochemical properties of the tumour cells rather than by the differences in blood supply per viable tumour cell. Biochemical properties of particular importance included rate of respiration, glycolytic capacity and tolerance to hypoxic stress. On the other hand, tumour bioenergetic status and tumour pH were correlated to blood supply per viable tumour cell within individual tumour lines. These observations suggest that 31P-NMR spectroscopy may be developed to be a clinically useful method for monitoring tumour blood supply and parameters related to tumour blood supply during and after physiological intervention and tumour treatment. However, clinically useful parameters for prediction of tumour treatment resistance caused by insufficient blood supply can probably not be derived from a single 31P-NMR spectrum since correlations across tumour lines were not detected; additional information is needed.

Energetics of nutrition and polyamine-related tumour growth alterations in experimental cancer

The aim of this study was to evaluate whether food intake modulates experimental tumour growth by acute alterations in the energy state and blood flow of the tumour, and if so whether such changes are related to alterations in the enzyme ornithinedecarboxylase (ODC) and DNA synthesis. Inbred mice (C57BL/J) bearing a syngeneic undifferentiated and rapidly growing tumour were used. The tumour levels of high energy phosphates were measured in vivo by 31-P-NMR spectroscopy and biochemically following tissue extraction. DNA synthesis was estimated by measuring the incorporation of bromodeoxy-uridine into tumour DNA. Difluoro-methylornithine (DFMO) was used to inhibit ODC-activity. Tumour blood flow was estimated by a 132Xe local clearance technique. Tumour progression was associated with a significant decrease in tumour tissue high energy phosphates. Acute starvation decreased DNA-synthesis and tumour energy charge as well as its PCr/Pi which were rapidly normalised during subsequent refeeding. These changes were related to similar alterations in tumour blood flow. The inorganic phosphate (Pi) resonance and the resonances in the phosphomonoester (PME) region were considerably increased in tumour tissue. Inhibition of ODC-activity by DFMO decreased DNA-synthesis, which was associated with a secondary increase in tumour high energy phosphates probably due to a lowered energy demand for tumour cell division. The results demonstrate that host undernutrition was translated into retarded tumour growth associated with a decrease in the energy state and blood flow of the tumour. The results have bearing for the evaluation and planning of all treatment protocols with potential influence on food intake in experimental tumour-bearing animals.

In Vivo Nuclear Magnetic Resonance Spectroscopy of Chicken Embryos from Two Broiler Strains of Varying Fat Content

In vivo nuclear magnetic resonance (NMR) imaging and spectroscopy techniques were used to monitor changes in P- and H-containing molecules in embryos of two broiler strains (30 and 31) differing genetically in fat content and ranging in age from 0 to 20 days of incubation. Chemical analysis showed that Strain 30 has more carcass fat than Strain 31 at market age (7 wk). Proton (1 H) and 31 P spectra were obtained on four eggs per strain at Days 0, 2, 4, 6, 8, 11, 12, 14, 16, 17, 19, and 20 of incubation. Fat:water, phosphomonoester (PME):phosphodiester (PDE), and adenosine triphosphate (ATP):PDE ratios were calculated. Chicks were hatched, grown to market weight (2,000 g for females and 2,300 g for males at 7 wk), and the whole intact carcasses were analyzed for crude fat.Hydrogen-1 NMR spectroscopy studies of incubated eggs indicated no significant difference (P > .05) in the fat:water ratio between the two strains. The difference in the PME:PDE ratios between the two strains as obtained by 31 P-NMR spectroscopy over all days of incubation analyzed was not significant (P > .05); however, there was a significant difference in this ratio between the two strains at Days 4, 6, and 11. Up to Day 16, Strain 30 had a slightly, but not significantly (P > .05), higher ATP:PDE ratio as shown on 31 P-NMR spectra, whereas after Day 17 the ATP:PDE ratio was significantly higher (P < .01) for Strain 31. Strain 31 birds had a significantly lower (P < .05) crude fat content. There was a significant difference (P < .05) in 7-wk carcass fat content between sexes, males having significantly (P < .01) less fat than females, which was correlated with a significantly higher (P < .01) ATP:PDE ratio in male embryos. It might be possible to use ATP:PDE ratios obtained during embryonic development by 31 P-NMR to select strains of birds for low fat content at market weight and to distinguish between sexes during late embryonic development.

Metabolic response to halothane in piglets susceptible to malignant hyperthermia: an in vivo 31P-NMR study.

Using in vivo 31P-nuclear magnetic resonance spectroscopy, we studied the skeletal muscle metabolism of 17 anesthetized malignant hyperthermia-susceptible piglets and 25 control piglets during and after a halothane stress test. At rest, the phosphocreatine- (PCr) to-ATP ratio was 12% higher in the anesthetized piglets than in the control piglets, which may reflect a higher proportion of fast glycolytic fibers in the former. About 15 min of halothane administration sufficed to provoke onset of a reaction, which was characterized by a reciprocal drop in PCr and an increase in Pi with commencing intracellular acidosis. Halothane was withdrawn after a 20% drop in PCr. Within the next few minutes, intracellular pH dropped sharply and phosphomonoesters (PME) accumulated excessively. ATP was observed to decrease in 8 of the 17 animals. Halothane inhalation provoked a switch of metabolism toward glycolysis. Accumulation of PME suggests a mismatch between glycogenolysis and glycolysis. Despite severe acidification, glycolysis was not completely halted. Recovery of PCr and Pi started approximately 5 min after halothane withdrawal, with a longer time constant for recovery of the former. PME and intracellular pH aberrations lingered and started to recover later. Lost ATP was never restored within the observed recovery period of approximately 20 min.

Metabolic changes in the rat brain after acute and chronic ethanol intoxication: A 31P NMR spectroscopy study

In this work, 31P phosphorus NMR (31P NMR) studies of the brain have been conducted in rats acutely and chronically intoxicated with ethanol. In both groups, changes in levels of high-energy phosphates were observed: increase of phosphocreatinine (PCr)/beta AaTP and PCr/inorganic phosphate (Pi) in acute and long-term ethanol exposure, and decrease of Pi/beta ATP after acute ethanol administration. These changes in high-energy phosphates, indicative of a reduction of adenosine triphosphate (ATP) and PCr consumption (PCr+ ADP+ H+ ATP+ Cr; ATP ADP+ Pi), suggest a reduction of cerebral metabolism both in acute and chronic ethanol exposure. In addition, in the group of rats chronically intoxicated with ethanol, there were variations in phosphodiester peak intensities (decrease of phosphomonoester (PME)/phosphodiester (PDE), increase of PDE/beta ATP), suggesting increased breakdown of membrane phospholipids. These changes could provide a metabolic explanation for the development of cerebral atrophy in chronic alcoholism.

Phosphomonoester is associated with proliferation in human breast cancer: a 31P MRS study

Phospholipid metabolism of human breast cancer was studied by 31P magnetic resonance spectroscopy (MRS). In vivo localised 31P MR spectra were obtained from the tumour alone using phase modulated rotating frame imaging. For 31 tumours, median (range) phosphomonoester (PME) to ATP ratio was 1.48 (0.57-3.78) and phosphodiester (PDE) to ATP ratio was 1.65 (0.44-3.89). DNA index and S phase fraction (SPF) were measured by flow cytometry of paraffin embedded tissue. Twelve (39%) tumours were diploid and 19 aneuploid. Median (range) SPF for 29 assessable tumours was 5.3% (0.6-28%), with significantly greater median SPF for aneuploid tumours (9.3%) than diploid (3.8%, P = 0.007). There was a significant association between PME/ATP and SPF (P = 0.03) due to a significant correlation for aneuploid tumours (P = 0.01). High resolution 31P MRS of extracts from 18 tumours (including seven studied in vivo) demonstrated that the PME peak consists predominantly of phosphoethanolamine (PE) with a smaller contribution from phosphocholine (PC) (median (range) PE/PC: 3.02 (1.13-5.09)). Changes in PME/ATP were observed for two tumours where tamoxifen stablized disease and may be consistent with the cytostatic effects of this drug.

Proton-decoupled 31P chemical shift imaging of the human brain in normal volunteers.

Proton-decoupled, 31P three-dimensional (3-D) chemical shift imaging (CSI) spectra have been acquired from the entire human brain using a new dual tuned resonator. The resonator operates in quadrature mode to provide improved sensitivity, excellent B1 homogeneity and reduced power deposition at both frequencies. Proton-decoupled and fully NOE enhanced, 31P spectra were acquired from normal volunteers using Waltz-4 proton decoupling with continuous wave bi-level excitation applied through a second radio frequency channel. Well resolved peaks in the phosphomonoester (PME) and phosphodiester regions were obtained from nonlocalized FIDs and spectra localized with 3-D CSI without processing for resolution enhancement. pH measurements made over large regions of the brain using the P(i) resonance show no significant variations (6.9 +/- 0.02) for a single individual. The improved spectral resolution and sensitivity of the PME resonances results in more well defined metabolite images of the PME peak region.

Alterations in brain phosphorous metabolism in bipolar disorder detected by in vivo 31P and 7Li magnetic resonance spectroscopy

Phosphorus-31 magnetic resonance spectroscopy (MRS), able to detect membrane metabolism and intracellular pH as well as energy metabolism in vivo, was applied to 17 bipolar patients in the manic state and the euthymic state. In nine of these patients, brain lithium concentration was simultaneously determined by means of lithium-7 MRS in order to clarify the effect of treatment with lithium on brain phosphorous metabolism. Both phosphomonoester (PME) peak area and intracellular pH were found to be higher in the manic state than in the euthymic state. These values in the euthymic state were lower than those in normal controls whose ages and sexes were matched with the patients. However, PME and intracellular pH did not correlate to brain lithium concentration. These findings coincide with a hypothesis that patients with bipolar disorder may have membrane abnormality in their euthymic state and state-dependent alteration of catecholaminergic activity may be a secondary phenomenon.

Determination of saturation factors in 31P NMR spectra of the developing human brain.

In order to assess the influence of longitudinal relaxation on previously reported variations in 31P NMR signals during brain development, we used an accelerated two-point technique to determine T1 at 2.35 Tesla in 8 min. Comparison between 10 normal neonates (age range 37-46 weeks postconception) and 10 healthy infants (age range 80-157 weeks postconception) indicated that T1 does not vary substantially during the first year of life, except in the phosphomonoester (PME) region of the spectra. T1 of total PME decreases with age which we could explain by its variable multicomponent nature: The signal from (unresolved) components at the downfield shoulder of PME (attributed mostly to phosphorylethanolamine at 6.72 ppm) with a T1 of at least 6.4 s decreases with age relative to contributions from other phosphomonoester compounds resonating predominantly at the upfield side of the peak (approximately 6.3 ppm), with T1 below 2.9 s. Because the T1 heterogeneity of PME may depend on its relative composition, quantitative 31P NMR spectroscopy may require an assessment of the influence of longitudinal relaxation on the signal amplitudes in each measurement.

Tumor growth retardation and pathophysiological effects of adenosine 5′‐triphosphate therapy measured by thallium washout, 31P nuclear magnetic resonance, laser doppler flowmetry, and intradermal angiogenesis

AbstractTransplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal (i.p.) adenosine 5′‐triphosphate (ATP) were studied in vitro, and in vivo in both C3H and nu/nu mice. In vivo daily ATP treatments caused a small dose‐dependent reduction in the total neovascular lumen area and thallium washout. There was an associated reduction in tumor volume doubling time but a similar growth rate reduction was also seen in vitro where flow has no impact. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH nuclear magnetic resonance or the phosphocreatine/inorganic phosphate (PCr/Pi), βATP/Pi, or phosphomonoester (PME)/ βATP ratios. The acute systemic physiological effects of i.p. ATP were mild, consisting of a transient reduction in skin laser Doppler flow and mean arterial pressure. Systemic toxicities of ATP given as daily boluses at doses capable of producing significant growth retardation of FSaII tumors were transient. Our results are most consistent with the hypothesis that the growth retarding effects of ATP are primarily a result of a decreased proliferation rather than tumor cytotoxicity or systemic pathophysiology. The main toxicity of ATP at active dose levels is cardiovascular. ATP might be useful as a biological modifier of chemotherapy or radiation. © 1994 Wiley‐Liss, IncThis article is a US Government work and, as such, is in the public domain in the United Stales of America. .

31P localized spectroscopy of fetal brain in utero.

31-Phosphorus (31P) nuclear magnetic resonance (NMR) spectroscopy of fetal brain in utero was obtained entirely noninvasively in rat utilizing image selected in vivo spectroscopy (ISIS). The results were in excellent agreement with the data obtained using the surface coil method in the late stage fetus, namely, high phosphomonoester (PME), low phosphocreatine (PCr), and high intracellular pH. Localized spectroscopy provides unprecedented opportunities for the investigation of fetal brain metabolism in utero.