Abstract
31P magnetic resonance spectroscopy (MRS) in vivo and in vitro was used to study modulation of host liver (HL) metabolism in rats bearing the MAT-LyLu variant of the Dunning prostate tumour. Animals were inoculated either with 10(6) or 10(7) MAT-LyLu cells, or with saline to serve as controls. Carcass weight in tumour-bearing (TB) animals decreased despite similar food and water intake in both groups. Absence of metastatic tumour cells from HL of all TB animals was confirmed by histological examination. Twenty-one days after inoculation, 31P MRS showed a 2.5-fold increase in [Pi]/[ATP] ratios in HL in vivo (P < 0.001) which was confirmed by 31P MRS of liver extracts in vitro (P < 0.005). Phosphodiester to ATP ratios were significantly increased (P < 0.05) in HL in vivo, but absolute PDE levels were similar in both groups. Phosphomonoester to ATP ratios did not change, although absolute phosphomonoester levels in HL were reduced by -41% (not significant). In HL extracts in vitro, sharp reductions in the levels of glucose-6-phosphate (P < 0.05), fructose-6-phosphate (P = 0.05), phosphocholine (P < 0.001), glycerophosphocholine (P < 0.001), and glycerophosphoethanolamine (P < 0.001) were observed. Electron microscopy revealed increased amounts and altered distribution of rough endoplasmic reticulum in HL. These findings show that experimental prostate cancer significantly affects hepatic phosphorylation status, phospholipid metabolism, and gluconeogenesis in the host animal, and demonstrate the value of combined MRS in vivo and in vitro in monitoring HL metabolism in cancer.
Highlights
Food and water intake of TB animals were within 10% of the control values, and no relation between these variables and test results was observed
Total body weight at the end of the study was similar in both groups of animals, but carcass weight of TB animals had decreased by 13 ± 2% during the 21-day study period, whereas body weight of NTB animals had increased by 7 ± 2%
This study has demonstrated modulation of hepatic energy and phospholipid metabolism to occur in the host livers of rats bearing the Dunning MAT-LyLu variant of prostatic cancer but in the absence of liver metastases
Summary
Animal preparationMAT-LyLu rat prostate carcinoma cells were obtained from Dr J. Adult male Copenhagen-Fisher Fl hybrid rats (Harlan-Olac Ltd, Bicester, Oxford, UK) were inoculated into subcutaneous tissues of the left flank with either I x 107 (experiment 1, n = 3) or 1 x 106 (experiment 2, n = 6) tumour cells suspended in 500 of sterile saline. Apart from the number of inoculated cells, the design of the two experiments was identical. Control animals were inoculated with saline (experiment 1: n = 4, experiment 2: n = 5). Thereafter, animals were maintained in adjacent individual cages with water and standard rat chow (Pilsbury's Ltd, Birmingham, UK) available ad libitum. Animals were maintained at 37°C throughout the experiment via a heated pad
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