Using Hoechst 33342 to Target Radioactivity to the Cell Nucleus

Yasui, Linda S.; Chen, Kai; Wang, Ketai; Jones, Tamera; Caldwell, James W.; Guse, Diana; Kassis, Amin I.

doi:10.1667/rr0584.1

Cited by 27 publications

(23 citation statements)

References 33 publications

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“…Many investigators have explored the relationship between g-H2AX foci formation and cytotoxicity for a variety of anticancer agents (17,26,27) including Auger electronemitting pharmaceuticals (28). In the current study, it has been demonstrated that a strong correlation between the number of g-H2AX foci and survival of breast cancer cells exposed to 111 In-DTPA-hEGF ( Fig.…”

Section: Discussionmentioning

confidence: 58%

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Cai

Chen²,

Bailey³

et al. 2008

J Nucl Med

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Section: Discussionmentioning

confidence: 58%

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Cai

Chen²,

Bailey³

et al. 2008

J Nucl Med

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“…T is agent produces efficient cell killing as predicted by theoretical dosimetry (Hofer and Hughes 1971, Feinendegen 1975, Chan et al 1976, Makrigiorgos et al 1989). Iodine-125-labeled DNA intercalators (Martin 1977, Kassis et al 1989), 125 I-labeled minor-groove binders, such as Hoechst 33342 and 33258 (Martin and Holmes 1983, Harapanhalli et al 1996, Kassis et al 1999a, 1999b, 2000, Balagurumoorthy et al 2006, Balagurumoorthy et al 2008a, 2008b, Yasui et al 2007), 123 I-labeled steroid hormones (DeSombre et al 1992, 2000, Yasui et al 1996, 2001), 125 I-deoxycytidine in homopyrimidine triplex-forming oligonucleotides (Panyutin et al 2000, 2001, Sedel-nikova et al 2000) and more recently 111 In conjugated to nuclear localization signal peptides (Costantini et al 2007, 2008) have also been used to position Auger-electron emitters proximal to DNA in the nucleus. The common property of all these agents is their ability to position the decaying atom within few nanometers distance from DNA within the mammalian cell nucleus.…”

Section: Introductionmentioning

confidence: 99%

Effect of distance between decaying¹²⁵I and DNA on Auger-electron induced double-strand break yield

Balagurumoorthy

Wang

et al. 2012

International Journal of Radiation Biology

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Purpose To determine the possible effects of 125I-to-DNA distance on the magnitude and mechanism of Auger-electron induced-double-strand break (DSB) production. Materials and methods We have synthesized a series of 125I-labeled Hoechst (H) derivatives (125IE–H, 125IB-H, 125I-C8-H and 125I-C12-H). While all four molecules share a common DNA minor groove binding bis-benzimidazole motif, they are designed to position 125I at varying distances from the DNA helix. Each Hoechst derivative was incubated at 4 °C in phosphate buffered saline (PBS) together with supercoiled (SC) 3H-pUC19 plasmid DNA (ratio 3:1) ± the •OH scavenger dimethyl sulfoxide (DMSO) (0.2 M). Aliquots were analyzed on agarose gels over time and DSB yields per decay of 125I atom were determined. Docking of the iodinated compounds on a DNA molecule was carried out to determine the distance between the iodine atom and the central axis of DNA. Results In the absence of DMSO, the results show that the DSB yields decrease monotonically as the 125I atom is distanced – by 10.5 Å to 13.9 Å – from the DNA helix (125IEH: 0.52 ± 0.01; 125IB– H: 0.24 ± 0.03; 125I-C8–H:0.18 ± 0.02; 125I-C12–H: 0.10 ± 0.00). In the presence of DMSO, DSB yields for 125IEH (0.49 ± 0.02) and 125IB-H (0.26 ± 0.04) remain largely unchanged indicating that DSB are entirely produced by direct effects. Strikingly, 125I-C8–H or 125I-C12 –H, did not produce detectable DSB in the presence of DMSO under similar conditions suggesting when 125I atom is positioned > 12 Å from the DNA, DSB are entirely produced by indirect effects. Conclusion These results suggest that at a critical distance between the 125I atom and the DNA helix, DSB production switches from an ‘all’ direct to an ‘all’ indirect mechanism, the latter situation being comparable to the decay of 125I free in solution. These experimental findings were correlated with theoretical expectations based on microdosimetry.

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“…They include a complexing agent for the radionuclide as a carrier for the transport through different cell barriers into the nuclei of living cells and a DNA-binding moiety. There are various studies in this field of science, for example, with oligonucleotides, 15,16 antibodies, 17 peptides, 18 molecules containing nuclei localisation sequences (NLS), 19 anthracenyl fragments, 20,21 desoxyuridine, 22 acridine derivatives, 18 and Hoechst derivatives 23,24 as carriers for different Auger emitters. Based on these results, we developed a new approach with DAPI, a commonly used fluorescent dye for staining cell nuclei, as a carrier for 99m Tc.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of a new HYNIC-DAPI derivative for labelling with ^99mTechnetium and its in vitro evaluation in an FRTL5 cell line

et al. 2015

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4′,6-Diamidine-2-phenylindole (DAPI) is a common fluorochrome that is able to bind to deoxyribonucleic acid (DNA) with distinct, sequence-dependent enhancement of fluorescence. This work presents the synthesis of a new multifunctional compound that includes the fluorescent dye as a 99m Technetium ( 99m Tc) carrier. A new technique for the bioconjugation of DAPI with 6-hydrazinonicotinic acid (HYNIC) through an amide linkage was developed. The radiolabelling was performed with HYNIC as a chelator and N-Ĳ2-hydroxy-1,1-bisĲhydroxymethyl)ethyl)glycine (tricine) as a coligand. Furthermore, experimental evidence showed that 99m Tc complexes with DAPI as DNA-binding moieties are detectable in living Fischer rat thyroid follicular cell line 5 (FRTL5) and their nuclei. The investigations indicated further that the new HYNIC-DAPI derivative is able to interact with double-stranded DNA. This establishes the possibility of locating 99m Tc in close proximity to biological structures of living cells, of which especially the genetic information-carrying cell compartments are at the centre of interest. In this context, further investigations are related to the radiotoxic effects of DNA-bound 99m Tc-HYNIC-DAPI derivatives and dosimetric calculations.

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Using Hoechst 33342 to Target Radioactivity to the Cell Nucleus

Cited by 27 publications

References 33 publications

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Effect of distance between decaying¹²⁵I and DNA on Auger-electron induced double-strand break yield

Synthesis of a new HYNIC-DAPI derivative for labelling with ^99mTechnetium and its in vitro evaluation in an FRTL5 cell line

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Using Hoechst 33342 to Target Radioactivity to the Cell Nucleus

Cited by 27 publications

References 33 publications

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to 111In-DTPA-hEGF

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to 111In-DTPA-hEGF

Effect of distance between decaying125I and DNA on Auger-electron induced double-strand break yield

Synthesis of a new HYNIC-DAPI derivative for labelling with 99mTechnetium and its in vitro evaluation in an FRTL5 cell line

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Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Relationship Between Induction of Phosphorylated H2AX and Survival in Breast Cancer Cells Exposed to ¹¹¹In-DTPA-hEGF

Effect of distance between decaying¹²⁵I and DNA on Auger-electron induced double-strand break yield

Synthesis of a new HYNIC-DAPI derivative for labelling with ^99mTechnetium and its in vitro evaluation in an FRTL5 cell line