Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism

William Ralph Vogler; Susan Horwitz; D. P. Groth

Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism

William Ralph Vogler, Susan Horwitz, D. P. Groth

Research output: Contribution to journal › Article › peer-review

Abstract

The reversal of azauridine-induced oroticaciduria by hydroxyurea has been studied to further elucidate the control mechanisms involved in the de novo pathways of pyrimidine biosynthesis. No direct effect of hydroxyurea upon partially purified aspartate transcarbamylase and dihydroorotase was observed. Hydroxyurea selectively inhibited the incorporation of ¹⁴C-labeled aspartate, orotate, and formate into the DNA bases of human leukemic cells incubated in vitro. No effect of hydroxyurea was observed in the RNA bases isolated from these leukemic cells. Other chemotherapeutic agents, including 5-iododeoxyuridine, 5-fluorodeoxyuridine, Methotrexate, cytosine arabinoside, and cyclophosphamide, were administered to patients receiving 6-azauridine. Only Methotrexate and cyclophosphamide inhibited orotic acid excretion in a manner similar to hydroxyurea. These results suggest that the control of pyrimidine biosynthesis is linked to DNA synthesis or function in an as yet unexplained manner.

Original language	English (US)
Pages (from-to)	1371-1378
Number of pages	8
Journal	Cancer research
Volume	29
Issue number	7
State	Published - Jul 1 1969
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Cite this

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title = "Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism",

abstract = "The reversal of azauridine-induced oroticaciduria by hydroxyurea has been studied to further elucidate the control mechanisms involved in the de novo pathways of pyrimidine biosynthesis. No direct effect of hydroxyurea upon partially purified aspartate transcarbamylase and dihydroorotase was observed. Hydroxyurea selectively inhibited the incorporation of 14C-labeled aspartate, orotate, and formate into the DNA bases of human leukemic cells incubated in vitro. No effect of hydroxyurea was observed in the RNA bases isolated from these leukemic cells. Other chemotherapeutic agents, including 5-iododeoxyuridine, 5-fluorodeoxyuridine, Methotrexate, cytosine arabinoside, and cyclophosphamide, were administered to patients receiving 6-azauridine. Only Methotrexate and cyclophosphamide inhibited orotic acid excretion in a manner similar to hydroxyurea. These results suggest that the control of pyrimidine biosynthesis is linked to DNA synthesis or function in an as yet unexplained manner.",

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T1 - Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism

AU - Vogler, William Ralph

AU - Horwitz, Susan

AU - Groth, D. P.

PY - 1969/7/1

Y1 - 1969/7/1

N2 - The reversal of azauridine-induced oroticaciduria by hydroxyurea has been studied to further elucidate the control mechanisms involved in the de novo pathways of pyrimidine biosynthesis. No direct effect of hydroxyurea upon partially purified aspartate transcarbamylase and dihydroorotase was observed. Hydroxyurea selectively inhibited the incorporation of 14C-labeled aspartate, orotate, and formate into the DNA bases of human leukemic cells incubated in vitro. No effect of hydroxyurea was observed in the RNA bases isolated from these leukemic cells. Other chemotherapeutic agents, including 5-iododeoxyuridine, 5-fluorodeoxyuridine, Methotrexate, cytosine arabinoside, and cyclophosphamide, were administered to patients receiving 6-azauridine. Only Methotrexate and cyclophosphamide inhibited orotic acid excretion in a manner similar to hydroxyurea. These results suggest that the control of pyrimidine biosynthesis is linked to DNA synthesis or function in an as yet unexplained manner.

AB - The reversal of azauridine-induced oroticaciduria by hydroxyurea has been studied to further elucidate the control mechanisms involved in the de novo pathways of pyrimidine biosynthesis. No direct effect of hydroxyurea upon partially purified aspartate transcarbamylase and dihydroorotase was observed. Hydroxyurea selectively inhibited the incorporation of 14C-labeled aspartate, orotate, and formate into the DNA bases of human leukemic cells incubated in vitro. No effect of hydroxyurea was observed in the RNA bases isolated from these leukemic cells. Other chemotherapeutic agents, including 5-iododeoxyuridine, 5-fluorodeoxyuridine, Methotrexate, cytosine arabinoside, and cyclophosphamide, were administered to patients receiving 6-azauridine. Only Methotrexate and cyclophosphamide inhibited orotic acid excretion in a manner similar to hydroxyurea. These results suggest that the control of pyrimidine biosynthesis is linked to DNA synthesis or function in an as yet unexplained manner.

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AN - SCOPUS:0014549373

SN - 0008-5472

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ER -

Studies on the Effects of Hydroxyurea and Other Anticancer Drugs upon Pyrimidine Metabolism

Abstract

ASJC Scopus subject areas

UN SDGs

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