The dNTP imbalance death.
The mechanism of intracellular deoxyribonucleoside-triphosphates (dNTP) pool imbalance-induced cell death in mouse FM3A (F28-7) cells was studied. When the cells were treated with 5-fluorodeoxyuridine (FdUrd), deoxyadenosine, 2-chlorodeoxyadenosine, or alpha,alpha-bis(2-hydroxy-6-isopropyltropon-3-yl)-4-methoxytolu ene, an imbalance in the cellular dNTP pool was induced. The imbalance was followed by DNA double-strand breaks and subsequent cell death. Fragmented DNA appeared to be approximately 100-200 kbp in size. The base of 5'-termini in the DNA were adenine and thymine. The endonuclease toward double stranded DNA has been found in a fraction of FdUrd treated cell lysate, and isolated using column chromatography. We propose the new mechanism dNTP pool imbalance induced cell death named; dNTP Imbalance Death.
Otani
M
M
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Yoshida
S
S
Yoshioka-Hiramoto
A
A
Nakazawa
T
T
Wataya
Y
Y
D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D051379:Mice
D003854:Deoxyribonucleotides; D004247:DNA; D004720:Endonucleases