Comparative studies of UV-induced DNA cleavage by structural isomers of an iodinated DNA ligand

Martin, Roger F.; Kelly, David P.; Roberts, M P; Green, A.; Denison, L.; Rose, M; Reum, Monica E.; Pardee, Marshall

doi:10.1016/0360-3016(94)90454-5

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…Far more biologically relevant is the Comet assay, which visualizes DNA damage in single cells arising from the exposure to various combinations of antioxidants and ROS [ 28 , 29 ].. Cells are embedded in agarose coated slides and subjected to electrolysis, which causes the negatively charged DNA to migrate towards the anode.…”

Section: Resultsmentioning

confidence: 99%

Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

Philpott

Lim

Ferguson

2009

IJMS

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DNA damage by reactive species is associated with susceptibility to chronic human degenerative disorders. Anthocyanins are naturally occurring antioxidants, that may prevent or reverse such damage. There is considerable interest in anthocyanic food plants as good dietary sources, with the potential for reducing susceptibility to chronic disease. While structure-activity relationships have provided guidelines on molecular structure in relation to free hydroxyl-radical scavenging, this may not cover the situation in food plants where the anthocyanins are part of a complex mixture, and may be part of complex structures, including anthocyanic vacuolar inclusions (AVIs). Additionally, new analytical methods have revealed new structures in previously-studied materials. We have compared the antioxidant activities of extracts from six anthocyanin-rich edible plants (red cabbage, red lettuce, blueberries, pansies, purple sweetpotato skin, purple sweetpotato flesh and Maori potato flesh) using three chemical assays (DPPH, TRAP and ORAC), and the in vitro Comet assay. Extracts from the flowering plant, lisianthus, were used for comparison. The extracts showed differential effects in the chemical assays, suggesting that closely related structures have different affinities to scavenge different reactive species. Integration of anthocyanins to an AVI led to more sustained radical scavenging activity as compared with the free anthocyanin. All but the red lettuce extract could reduce endogenous DNA damage in HT-29 colon cancer cells. However, while extracts from purple sweetpotato OPEN ACCESSInt. J. Mol. Sci. 2009, 10 1082 skin and flesh, Maori potato and pansies, protected cells against subsequent challenge by hydrogen peroxide at 0 o C, red cabbage extracts were pro-oxidant, while other extracts had no effect. When the peroxide challenge was at 37 o C, all of the extracts appeared prooxidant. Maori potato extract, consistently the weakest antioxidant in all the chemical assays, was more effective in the Comet assays. These results highlight the dangers of generalising to potential health benefits, based solely on identification of high anthocyanic content in plants, results of a single antioxidant assay and traditional approaches to structure activity relationships. Subsequent studies might usefully consider complex mixtures and a battery of assays.

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Section: Resultsmentioning

confidence: 99%

Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

Philpott

Lim

Ferguson

2009

IJMS

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“…Comparison of o-, m-and p-iodoHoechst with respect to DNA strand breakage in plasmid DNA indicated remarkable differences in photopotency [13]. The ortho isomer was found to be more efficient than the meta and para isomers [14,15]. Moreover, the photo-induced cytotoxicity by these analogues in K562 cells also displays similar results [16].…”

Section: Introductionmentioning

confidence: 51%

Assessment of molecular binding of Hoechst 33258 analogues into DNA using docking and MM/GBSA approach

Issar

Kumari

Kakkar

2015

Journal of Computational Science

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“…Studies have highlighted the photopotency of directly iodinated Hoechst 33258 (prepared by direct iodination of the commercially available Hoechst 33258) and in particular the three structural isomers designated ortho-, meta-, and para-iodo-Hoechst reflecting the position of the iodine substitution on the terminal ring. The ortho-analogue-subsequently referred to as UV A Sens (Figure 1)-has shown remarkable photoefficiency, approximately 1000-fold greater potency than that of the clinically used psoralens [18,19]. Upon UV A irradiation, UV A Sens is rapidly dehalogenated to phenyl Hoechst, creating a carbon-centered radical which is analogous to the uracilyl radical produced from the halogenated DNA precursors [17].…”

Section: Introductionmentioning

confidence: 99%

Combination Phototherapy with a Histone Deacetylase Inhibitor and a Potent DNA-Binding Bibenzimidazole: Effects in Haematological Cell Lines

2012

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Current treatment for cutaneous T-cell lymphoma includes phototherapy, which involves either the use of narrowband ultraviolet B light or UV A in combination with a psoralen photosensitiser. Therapy typically involves administration of the photosensitiser followed by topical exposure to UV A . A different approach is extracorporeal photopheresis, an ex vivo strategy which is used for more advanced stages of disease. Further, histone deacetylase inhibitors are emerging as potent anticancer agents with suberoylanilide hydroxamic acid and depsipeptide, having received FDA approval for the treatment of cutaneous T-cell lymphoma. We have developed UV A Sens, an extremely potent, DNA minor groove-binding UV A sensitizer for potential use in phototherapy. We have previously demonstrated the extreme photopotency of UV A Sens in human erythroleukemic K562 cells. Here we have extended those studies by investigating the photopotency of UV A Sens in four haematological cell lines, namely, K562, T-cell leukaemic CEM-CCRF, P-glycoprotein overexpressing R100, and transformed B-lymphoblastoid cell lines (LCL) cells. In addition, we investigated the effects of suberoylanilide hydroxamic acid in combination with UV A Sens. Using γH2AX as the endpoint, our findings indicate that UV A Sens-induced phototoxicity in all four of the haematological cell lines. The addition of suberoylanilide hydroxamic acid augmented the photopotency of UV A Sens highlighting the potential clinical applicability of combination therapies.

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Comparative studies of UV-induced DNA cleavage by structural isomers of an iodinated DNA ligand

Cited by 10 publications

References 31 publications

Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

Dietary Protection Against Free Radicals: A Case for Multiple Testing to Establish Structure-activity Relationships for Antioxidant Potential of Anthocyanic Plant Species

Assessment of molecular binding of Hoechst 33258 analogues into DNA using docking and MM/GBSA approach

Combination Phototherapy with a Histone Deacetylase Inhibitor and a Potent DNA-Binding Bibenzimidazole: Effects in Haematological Cell Lines

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