TY - JOUR
T1 - Fe (ii)-chelates based on redox-active pyridoxal-betaines as c-centered radicals causing single- and double-Strand scissions to dna
AU - Iheanacho, Eugene N.
AU - Sarel, Shalom
AU - Samuni, Amram
AU - Avramovici-Grisaru, Shelly
AU - Spira, Dan T.
PY - 1991
Y1 - 1991
N2 - The ability of 1-[N-Ethoxycarbonylmethylpridoxylidenium]-2-[2-pyridyljhydrazine bromide code name-[L2-9 = L+, X-]-FE(II) chelate [L2-9-Fe(II)] to induce breaks both in the 43kb linear double-strandphage DNA, and in the 4363 base pair supercoiled pBR322 plasmid DNA is herein described. Neither the free ligand nor FE(II) alone demonstrated any effect on the DNA. The cleaving ability is shown to occur instantaneously under strictly anaerobic conditions, either in the presence or absence of the enzyme catalase. It is also shown to be dose dependent. Thus, atDNA: L2-9-Fe(II) molar ratio of 3.7: 1.0, the linear DNA is randomly cleaved into fragments ranging from 23. Ikb to 4.3kb, whereas at approximately 1: 1 molar ratio, the range extends down to 2.5kb fragments. By contrast, at 1: 2.7 [plasmid DNA]: chelate-Fe(II). molar ratio, a single-strand nick was observed, and a double strand break was noted at a 1: 50 ratio ([plasmid DNA]: chelate-Fe(II). A multi-stage redox cycling involving a carbon-centered (L, X-)-Fe(III) radical capable of transferring an electron to the DNA to form high unstable [DNA]- anion-radical is invoked to explain the degradation of the chain macromolecule. Possible modes for regeneration of the chelate-Fe(III) radical both at the cell-free and at the cell levels are proposed.
AB - The ability of 1-[N-Ethoxycarbonylmethylpridoxylidenium]-2-[2-pyridyljhydrazine bromide code name-[L2-9 = L+, X-]-FE(II) chelate [L2-9-Fe(II)] to induce breaks both in the 43kb linear double-strandphage DNA, and in the 4363 base pair supercoiled pBR322 plasmid DNA is herein described. Neither the free ligand nor FE(II) alone demonstrated any effect on the DNA. The cleaving ability is shown to occur instantaneously under strictly anaerobic conditions, either in the presence or absence of the enzyme catalase. It is also shown to be dose dependent. Thus, atDNA: L2-9-Fe(II) molar ratio of 3.7: 1.0, the linear DNA is randomly cleaved into fragments ranging from 23. Ikb to 4.3kb, whereas at approximately 1: 1 molar ratio, the range extends down to 2.5kb fragments. By contrast, at 1: 2.7 [plasmid DNA]: chelate-Fe(II). molar ratio, a single-strand nick was observed, and a double strand break was noted at a 1: 50 ratio ([plasmid DNA]: chelate-Fe(II). A multi-stage redox cycling involving a carbon-centered (L, X-)-Fe(III) radical capable of transferring an electron to the DNA to form high unstable [DNA]- anion-radical is invoked to explain the degradation of the chain macromolecule. Possible modes for regeneration of the chelate-Fe(III) radical both at the cell-free and at the cell levels are proposed.
KW - DNA breakage
KW - Free radicals
KW - Iron chelates
UR - http://www.scopus.com/inward/record.url?scp=0025924607&partnerID=8YFLogxK
U2 - 10.3109/10715769109088928
DO - 10.3109/10715769109088928
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C2 - 2071028
AN - SCOPUS:0025924607
SN - 1071-5762
VL - 11
SP - 307
EP - 315
JO - Free Radical Research
JF - Free Radical Research
IS - 6
ER -