scholarly journals Dissociations of free radicals to generate protons, electrophiles or nucleophiles: role in DNA strand breaks

2021 ◽  
Author(s):  
John C. Walton
Keyword(s):  
Free Radicals ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Radical Generation ◽  
Dna Strand

The concept behind the research described in this article was that of marrying the ‘soft’ methods of radical generation with the effectiveness and flexibility of nucleophile/electrophile synthetic procedures.

Binding affinity of Cu(II)–VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation During DNA strand breaks

1998 ◽  
Vol 6 (7) ◽  
pp. 1003-1008 ◽  
Author(s):  
Riichi Tawa ◽  
Dayuan Gao ◽  
Masashi Takami ◽  
Yasuhiro Imakura ◽  
Kuo-Hsiung Lee ◽  
...  
Keyword(s):  
Hydroxyl Radical ◽  
Binding Affinity ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Radical Generation ◽  
Dna Strand

Asbestos causes DNA strand breaks in cultured pulmonary epithelial cells: role of iron-catalyzed free radicals

1995 ◽  
Vol 268 (3) ◽  
pp. L471-L480 ◽  
Author(s):  
D. W. Kamp ◽  
V. A. Israbian ◽  
S. E. Preusen ◽  
C. X. Zhang ◽  
S. A. Weitzman
Keyword(s):  
Dna Damage ◽  
Free Radicals ◽  
Free Radical ◽  
Phytic Acid ◽  
Dna Strand Breaks ◽  
Alveolar Type ◽  
Strand Breaks ◽  
Mineral Dusts ◽  
Dna Strand ◽  
Dose Dependent

Asbestos causes pulmonary fibrosis and various malignancies by mechanisms that remain uncertain. Reactive oxygen species in part cause asbestos toxicity. However, it is not known whether asbestos-induced free radical production causes alveolar epithelial cell (AEC) cytotoxicity by inducing DNA strand breaks (DNA-SB). We tested the hypothesis that asbestos-induced AEC injury in vitro is due to iron-catalyzed free radical generation, which in turn causes DNA-SB. We found that amosite asbestos damages cultured human pulmonary epithelial-like cells (WI-26 cells) as assessed by 51Cr release and that an iron chelator, phytic acid (500 microM), attenuates these effects. A role for iron causing these effects was supported by the observation that ferric chloride-treated phytic acid did not diminish WI-26 cell injury. Production of hydroxyl radical-like species (.OH) was assessed based upon the .OH-dependent formation of formaldehyde (HCHO) in the presence of dimethyl sulfoxide. A variety of mineral dusts induced significant levels of .OH formation (nmol HCHO at 30 min: carbonyl iron, 85 +/- 21; amosite asbestos, 14 +/- 2; chrysotile asbestos, 7 +/- 1; titanium dioxide, 2.5 +/- 0.5). Phytic acid significantly diminished the asbestos-induced .OH production. DNA damage to AEC was assessed by the alkaline unwinding, ethidium bromide fluorometric technique. Hydrogen peroxide caused dose-dependent DNA-SB in WI-26 cells after a 30-min exposure period [50% effective dose (ED50): 5 microM] that was similar to other cell lines. Amosite asbestos induced dose-dependent DNA-SB in WI-26, A549, and primary isolated rat alveolar type II cells maintained in culture for 7-10 days (alveolar type I-like). Lower doses of amosite (0.5-5 micrograms/ml or 0.25-2.5 micrograms/cm2) caused significant WI-26 cell DNA-SB after prolonged exposure periods (> or = 2 days). Phytic acid ameliorated DNA damage in all three cultured AEC. There was a direct correlation between mineral dust-induced .OH production at 30 min and DNA-SB in WI-26 cells at 4 h (P < 0.0005). These data suggest that mineral dusts can be directly genotoxic to relevant target cells of asbestos, AEC. Furthermore, these results provide additional support for the premise that iron-catalyzed free radicals mediate asbestos-induced pulmonary toxicity.

scholarly journals Repair of DNA Strand Breaks by the Overlapping Functions of Lesion-Specific and Non-Lesion-Specific DNA 3′ Phosphatases

2001 ◽  
Vol 21 (21) ◽  
pp. 7191-7198 ◽  
Author(s):  
John R. Vance ◽  
Thomas E. Wilson
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Synthetic Lethality ◽  
Dna Strand Breaks ◽  
Triple Mutant ◽  
Phosphatase Domain ◽  
Strand Breaks ◽  
Alternative Pathways ◽  
Processing Enzymes ◽  
Dna Strand

ABSTRACT In Saccharomyces cerevisiae, the apurinic/apyrimidinic (AP) endonucleases Apn1 and Apn2 act as alternative pathways for the removal of various 3′-terminal blocking lesions from DNA strand breaks and in the repair of abasic sites, which both result from oxidative DNA damage. Here we demonstrate that Tpp1, a homologue of the 3′ phosphatase domain of polynucleotide kinase, is a third member of this group of redundant 3′ processing enzymes. Unlike Apn1 and Apn2, Tpp1 is specific for the removal of 3′ phosphates at strand breaks and does not possess more general 3′ phosphodiesterase, exonuclease, or AP endonuclease activities. Deletion ofTPP1 in an apn1 apn2 mutant background dramatically increased the sensitivity of the double mutant to DNA damage caused by H2O2 and bleomycin but not to damage caused by methyl methanesulfonate. The triple mutant was also deficient in the repair of 3′ phosphate lesions left by Tdp1-mediated cleavage of camptothecin-stabilized Top1-DNA covalent complexes. Finally, the tpp1 apn1 apn2 triple mutation displayed synthetic lethality in combination with rad52, possibly implicating postreplication repair in the removal of unrepaired 3′-terminal lesions resulting from endogenous damage. Taken together, these results demonstrate a clear role for the lesion-specific enzyme, Tpp1, in the repair of a subset of DNA strand breaks.

Sign in / Sign up

Export Citation Format

Share Document