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Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative

The mechanism by which α,α‐bis(2‐hydroxy‐6‐isopropyltropon‐3‐yl)‐4‐methoxytoluene (JCI‐3661) kills mouse mammary tumor FM3A (F28–7) cells was studied. When the cells were exposed to the drug at 3.7 μM, the intracellular dNTP pool became unbalanced because of decreases in dGTP and dATP and an increas...

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Autores principales: Yamato, Masatoshi, Hirota, Yasuhide, Yoshida, Sei, Tanaka, Shouhei, Morita, Tetsuo, Sakai, Junko, Hashigaki, Kuniko, Hayatsu, Hikoya, Wataya, Yusuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1992
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918875/
https://www.ncbi.nlm.nih.gov/pubmed/1644668
http://dx.doi.org/10.1111/j.1349-7006.1992.tb00141.x
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author Yamato, Masatoshi
Hirota, Yasuhide
Yoshida, Sei
Tanaka, Shouhei
Morita, Tetsuo
Sakai, Junko
Hashigaki, Kuniko
Hayatsu, Hikoya
Wataya, Yusuke
author_facet Yamato, Masatoshi
Hirota, Yasuhide
Yoshida, Sei
Tanaka, Shouhei
Morita, Tetsuo
Sakai, Junko
Hashigaki, Kuniko
Hayatsu, Hikoya
Wataya, Yusuke
author_sort Yamato, Masatoshi
collection PubMed
description The mechanism by which α,α‐bis(2‐hydroxy‐6‐isopropyltropon‐3‐yl)‐4‐methoxytoluene (JCI‐3661) kills mouse mammary tumor FM3A (F28–7) cells was studied. When the cells were exposed to the drug at 3.7 μM, the intracellular dNTP pool became unbalanced because of decreases in dGTP and dATP and an increase in dTTP. The pattern of the dNTP imbalance was the same as that caused by hydroxyurea. When JCI‐3661 was added to the culture medium, mature DNA strands broke, giving fragments of 100–200 kilobase pairs long as found by orthogonal‐field‐alternation gel electrophoresis. DNA strand breaks, detected by this technique, were observed in the cells at 12 h after the addition. The beginning of cell death was observed at about 14 h (trypan blue staining) or at about 12 h (colony‐forming ability) after cultivation Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution assay, became evident 24 h after treatment with 3.7 μM JCI‐3661. Comparison of the ratio of single‐ and double‐strand breaks caused by JCI‐3661 to that following radiation suggested that JCI‐3661 broke only double strands. Cycloheximide inhibited both the breakage of double strands and the cell death caused by JCI‐3661. JCI‐3661 decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by JCI‐3661.
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spelling pubmed-59188752018-05-11 Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative Yamato, Masatoshi Hirota, Yasuhide Yoshida, Sei Tanaka, Shouhei Morita, Tetsuo Sakai, Junko Hashigaki, Kuniko Hayatsu, Hikoya Wataya, Yusuke Jpn J Cancer Res Article The mechanism by which α,α‐bis(2‐hydroxy‐6‐isopropyltropon‐3‐yl)‐4‐methoxytoluene (JCI‐3661) kills mouse mammary tumor FM3A (F28–7) cells was studied. When the cells were exposed to the drug at 3.7 μM, the intracellular dNTP pool became unbalanced because of decreases in dGTP and dATP and an increase in dTTP. The pattern of the dNTP imbalance was the same as that caused by hydroxyurea. When JCI‐3661 was added to the culture medium, mature DNA strands broke, giving fragments of 100–200 kilobase pairs long as found by orthogonal‐field‐alternation gel electrophoresis. DNA strand breaks, detected by this technique, were observed in the cells at 12 h after the addition. The beginning of cell death was observed at about 14 h (trypan blue staining) or at about 12 h (colony‐forming ability) after cultivation Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution assay, became evident 24 h after treatment with 3.7 μM JCI‐3661. Comparison of the ratio of single‐ and double‐strand breaks caused by JCI‐3661 to that following radiation suggested that JCI‐3661 broke only double strands. Cycloheximide inhibited both the breakage of double strands and the cell death caused by JCI‐3661. JCI‐3661 decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by JCI‐3661. Blackwell Publishing Ltd 1992-06 /pmc/articles/PMC5918875/ /pubmed/1644668 http://dx.doi.org/10.1111/j.1349-7006.1992.tb00141.x Text en
spellingShingle Article
Yamato, Masatoshi
Hirota, Yasuhide
Yoshida, Sei
Tanaka, Shouhei
Morita, Tetsuo
Sakai, Junko
Hashigaki, Kuniko
Hayatsu, Hikoya
Wataya, Yusuke
Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title_full Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title_fullStr Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title_full_unstemmed Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title_short Imbalance of Deoxyribonucleoside Triphosphates and DNA Double‐strand Breaks in Mouse Mammary Tumor FM3A Cells Treated in vitro with an Antineoplastic Tropolone Derivative
title_sort imbalance of deoxyribonucleoside triphosphates and dna double‐strand breaks in mouse mammary tumor fm3a cells treated in vitro with an antineoplastic tropolone derivative
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918875/
https://www.ncbi.nlm.nih.gov/pubmed/1644668
http://dx.doi.org/10.1111/j.1349-7006.1992.tb00141.x
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