Heat Radiosensitization and the Level of DNA Polymerases α and β of Human Colony-forming Unit-Granulocyte-Macrophage and Myeloid Leukemias Sensitive and Resistant to Chemotherapeutic Agents

Nahid F Mivechi, Hayato Miyachi, Kevin J. Scanlon

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Abstract

In these studies, heat radiosensitization in normal human colony-forming unit-granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases α and β in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 132 ± 0.2 Gy and TER of 1.4. However, in contrast to normal CFU-GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (D,) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as l- β-Z)-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 ± 0.13, and 1.77 ± 0.18 Gy; D., of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases α and β activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase β after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug-resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase β activity results in a higher amount of heat radiosensitization.

Original languageEnglish (US)
Pages (from-to)2044-2048
Number of pages5
JournalCancer Research
Volume50
Issue number7
StatePublished - Apr 1 1990
Externally publishedYes

Fingerprint

Granulocyte-Macrophage Progenitor Cells
Myeloid Leukemia
DNA-Directed DNA Polymerase
Hot Temperature
K562 Cells
X-Rays
Etoposide
Pharmaceutical Preparations
Cytarabine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

@article{3a9c01a1fa5f462a95b08c221d361b0e,
title = "Heat Radiosensitization and the Level of DNA Polymerases α and β of Human Colony-forming Unit-Granulocyte-Macrophage and Myeloid Leukemias Sensitive and Resistant to Chemotherapeutic Agents",
abstract = "In these studies, heat radiosensitization in normal human colony-forming unit-granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases α and β in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 132 ± 0.2 Gy and TER of 1.4. However, in contrast to normal CFU-GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (D,) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as l- β-Z)-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 ± 0.13, and 1.77 ± 0.18 Gy; D., of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases α and β activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase β after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug-resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase β activity results in a higher amount of heat radiosensitization.",
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T1 - Heat Radiosensitization and the Level of DNA Polymerases α and β of Human Colony-forming Unit-Granulocyte-Macrophage and Myeloid Leukemias Sensitive and Resistant to Chemotherapeutic Agents

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AU - Miyachi, Hayato

AU - Scanlon, Kevin J.

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N2 - In these studies, heat radiosensitization in normal human colony-forming unit-granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases α and β in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 132 ± 0.2 Gy and TER of 1.4. However, in contrast to normal CFU-GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (D,) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as l- β-Z)-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 ± 0.13, and 1.77 ± 0.18 Gy; D., of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases α and β activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase β after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug-resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase β activity results in a higher amount of heat radiosensitization.

AB - In these studies, heat radiosensitization in normal human colony-forming unit-granulocyte-macrophage (CFU-GM) and several different leukemic cell lines sensitive or resistant to chemotherapeutic agents were measured. Extent of heat radiosensitization was then correlated with the level of DNA polymerases α and β in control and heat-shocked cells in order to examine whether there is a positive correlation between the degree of heat radiosensitization and the level of these enzymes. Our results show that human bone marrow CFU-GM have an x-ray response with D0 of 1.56 Gy and a small amount of heat radiosensitization with a thermal enhancement ratio (TER) of 1.2. K562, a human erythroleukemic cell, showed a D0 of 132 ± 0.2 Gy and TER of 1.4. However, in contrast to normal CFU-GM which showed no shoulder in the X-ray survival curve, K562 cells showed a small shoulder with a quasi-threshold dose, (D,) of 2 Gy and n of 2. K562 cells resistant to chemotherapeutic drugs such as l- β-Z)-arabinofuranosylcytosine and etoposide (VP-16) showed D0 of 1.47 ± 0.13, and 1.77 ± 0.18 Gy; D., of 4 and 0 Gy; and n of 5 and 1; and TER of 1.6 and 2, respectively. The level of DNA polymerases α and β activity and their respective mRNA levels were approximately the same in all cells. The reduction in the level of DNA polymerase β after heat treatment however, correlated with the TER obtained for various leukemic cells. These studies indicate that normal CFU-GM and variety of human leukemic cells show only a small amount of heat radiosensitization. However, drug-resistant leukemic cells show a higher amount of heat radiosensitization than their drug-sensitive parent line. This suggests that hyperthermia may be beneficial in eradicating drug-resistant leukemic cells when combined with X-ray. Furthermore, the inactivation of DNA polymerase β activity results in a higher amount of heat radiosensitization.

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