Effects of Hydroxyurea and 6-Mercaptopurine on Growth and Some Aspects of Carbohydrate Metabolism in Regenerating and Neoplastic Liver

M. A. Lea, D. Sasovetz, A. Musella, H. P. Morris

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21 Scopus citations

Abstract

Previous observations have shown changes in several pathways of carbohydrate metabolism in a variety of hepatomas. Glycogen levels and the activities of the glycolytic enzymes causing the phosphorylation of glucose and fructose 6-phosphate were chosen as important examples of such changes, and a study was made to observe how closely the alterations were related to changes in growth rate. Growth in regenerating and neoplastic liver of rats was measured by the increase in tissue weight and by DNA synthesis. Daily administration of hydroxyurea (250 or 1000 mg/kg) and 6-mercaptopurine (10 or 45 mg/kg) had a greater effect on the inhibition of DNA synthesis than on liver weight or liver/body weight ratios for regenerating liver. The depletion of glycogen in this tissue either was not affected or was increased by administration of the two compounds. The high dose level of 6-mercaptopurine blocked the increase in the activity of low-Km hexokinase in regenerating liver. Hydroxyurea was a very effective inhibitor of thymidine-3 H incorporation into DNA in four hepatoma lines (7800, 5123-D, 7777, and 3924-A). Time-course studies showed a rapid recovery from the inhibition of DNA synthesis. The administration of six injections of hydroxyurea (1000 mg/kg) at 5-hr intervals was found to cause a 30% reduction in DNA concentration and a 27% decrease in phosphofructokinase activity in hepatoma 7777. A significant reduction in low-Km hexokinase activity was also observed. Under the conditions used, no tendency was observed for a restoration of high-Km glucokinase activity in hepatomas after a decrease in growth rate.

Original languageEnglish (US)
Pages (from-to)1994-1999
Number of pages6
JournalCancer Research
Volume30
Issue number7
StatePublished - Jul 1970

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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