TY - JOUR
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
AU - Mivechi, Nahid F.
AU - Miyachi, Hayato
AU - Scanlon, Kevin J.
PY - 1990/4/1
Y1 - 1990/4/1
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.
UR - http://www.scopus.com/inward/record.url?scp=0025237154&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025237154&partnerID=8YFLogxK
M3 - Article
C2 - 2317794
AN - SCOPUS:0025237154
SN - 0008-5472
VL - 50
SP - 2044
EP - 2048
JO - Cancer Research
JF - Cancer Research
IS - 7
ER -