Incorporation of Precursors and Inhibitors of Nucleic Acid Synthesis into Hepatomas and Liver of the Rat

M. A. Lea, J. Bullock

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In order to evaluate the entry of nucleic acid precursors into transplanted hepatomas and to examine the relationship to growth rate, the incorporation of isotope label was measured in tissue fractions. The low rate of incorporation of orotate into RNA of hepatomas in comparison with liver was confirmed and found to occur even in the most slowly growing tumors. A similar pattern was observed for the incorporation of orotate into the acid-soluble fraction. Under appropriate conditions, all the hepatomas examined were able to achieve an orotate incorporation greater that that in blood and several other tissues. Similar data were obtained 60 min after either i.p. or s.c. injections. Studies with several other molecules including dihydroorotate, uracil, uridine, thymidine, inorganic phosphate, 5-fluorouracil, and hycanthone did not show such pronounced changes in hepatomas but did suggest that uptake of these compounds is less in more rapidly growing liver tumors than in the slowly growing tumors. From the unequal incorporation of different molecules into a given tumor, from temporal studies of uptake, and from a comparative uptake study of s.c. and intrahepatic tumors, it was concluded that the vascular supply was not the sole determinant for the relative uptake of orotate in different tumor tissues. The data suggested that a transport mechanism for orotate may be impaired in hepatic neoplasia. As the regenerating liver did not show this transition, it does not appear to be an essential feature of cellular proliferation.

Original languageEnglish (US)
Pages (from-to)3414-3420
Number of pages7
JournalCancer Research
Issue number12
StatePublished - Dec 1974

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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