Abstract
Enzymatic, and microbiological assays were used to determine the hepatic contents of coenzyme A, acetyl CoA, fatty acid synthetase activity, and pantothenate in livers of tumour-bearing mice. Significant decreases in CoA and acetyl CoA were found in mice bearing TLX-5 lymphoma, sarcoma 180 or a fibrosarcoma. These changes were accompanied by significant decreases in pantothenate and increases in 4-phosphopantothenate suggesting an increase in pantothenate kinase activity due to reduction of CoA inhibition of the enzyme. In contrast, large increases were found in pantothenate and 4-phosphopantothenate in mice bearing TLX-5 lymphoma, i.p. or s.c. These changes could be due to a large reduction in the rate of conversion of an intermediate in the pathway of CoA, or increased production of pantothenate or 4-phosphopantothenate from the degradation of CoA or the phosphopantetheine residue in fatty acid synthetase. Activities of fatty acid synthetase in liver of mice bearing this tumour showed marked decreases, but were insufficient to account for the increase in pantothenate, and may reflect a reduction in cytosolic CoA needed for the conversion of the apo to the holoenzyme.
Highlights
A mouse fibrosarcoma in C57 mice was maintained in the same way, and by the same route in groups of recipients
Tumour-bearers and their corresponding controls were killed by cervical dislocation at the following times after implant: TLX-5 lymphoma, 6 days; sarcoma 180, 10 days and fibrosarcoma groups, 13 days
After further cooling in ice for 10min followed by centrifugation, aliquots of the supernatants were used for the determination of CoASH and acetyl CoA by a specific enzymatic method (Moellering & Bergmeyer, 1965)
Summary
Three to 4 month old male mice were used throughout. AllCorrespondence: R.A. Groups of 6 mice received 2 x 106 cells in 0.5 ml of medium either i.p. or s.c. in the subscapular region under light ether anaesthesia. Sarcoma 180 was maintained in BALB/c mice This tumour had been implanted 10 days previously s.c. in the subscapular region under light ether anaesthesia. Donor animals were killed by cervical dislocation, and the tumours dissected free from necrotic areas, cut into small pieces (-2mm) which were inserted into groups of 6 mice by the same route, under anaesthesia. Tumour-bearers and their corresponding controls were killed by cervical dislocation at the following times after implant: TLX-5 lymphoma, 6 days; sarcoma 180, 10 days and fibrosarcoma groups, 13 days.
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