Deoxyribonucleoside-triphosphate imbalance death: deoxyadenosine-induced dNTP imbalance and DNA double strand breaks in mouse FM3A cells and the mechanism of cell death.
The mechanism of deoxyadenosine (dAdo)-induced death of mouse mammary tumor FM3A cells was studied. When the cells were exposed to dAdo at 3 mM, an imbalance of intracellular dNTP pool resulted: dATP concentration was elevated 100-fold and the dGTP concentration was reduced to less than 1% of the control values. The imbalance was followed by breakage of mature DNA. DNA double strand breaks were observed in the dAdo treated cells 12 hr after the administration. We assume that the double strand breaks play an important role in the process of the dAdo-mediated cell death, and that the intracellular dNTP imbalance is the trigger of these events.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D004247:DNA / Q000187:drug effects*; D003839:Deoxyadenosines / Q000494:pharmacology*; D003845:Deoxycytosine Nucleotides / Q000378:metabolism; D003853:Deoxyribonucleosides / Q000378:metabolism*; D051379:Mice; D009690:Nucleic Acid Conformation / Q000187:drug effects; D013942:Thymine Nucleotides / Q000378:metabolism; D013997:Time Factors
D003839:Deoxyadenosines; D003845:Deoxycytosine Nucleotides; D003853:Deoxyribonucleosides; D013942:Thymine Nucleotides; C024107:2'-deoxycytidine 5'-triphosphate; D004247:DNA; C024157:thymidine 5'-triphosphate