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Title: Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes

Abstract

This study assessed the ability of 11 established and potential radiosensitizing agents to retard the repair of radiation-induced DNA damage with a view to enhancing the immunosuppressive effects of in vivo lymphoid irradiation. The capability of irradiated rat thymocytes to repair DNA damage was assessed by an adaptation of the fluorimetric unwinding method. Three compounds, 3-aminobenzamide (3-AB), novobiocin and flavone-8-acetic acid (FAA), inhibited repair significantly. We also report the effect of low-dose irradiation combined with repair inhibitors on the relationship between DNA strand breaks, fragmentation, cell viability and use of nicotinamide adenine dinucleotide (NAD). DNA fragmentation was increased by 1 mM/l FAA, 1 mM/l novobiocin and 50 {mu}M/l RS-61443 within 3 h of incubation. The latter two compounds also proved cytotoxic. All three drugs augmented the effect of ionizing radiation on the use of NAD. Of the agents investigated, FAA showed the most promise for augmenting the immunosuppressive action of irradiation at nontoxic, pharmacokinetically achievable concentrations. 33 refs., 1 fig., 2 tabs.

Authors:
;  [1]
  1. Univ. of the Witwatersrand Medical School, Johannesburg (South Africa)
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
45269
Resource Type:
Journal Article
Journal Name:
Radiation Research
Additional Journal Information:
Journal Volume: 137; Journal Issue: 1; Other Information: PBD: Jan 1994
Country of Publication:
United States
Language:
English
Subject:
56 BIOLOGY AND MEDICINE, APPLIED STUDIES; 55 BIOLOGY AND MEDICINE, BASIC STUDIES; DNA; RADIATION INJURIES; DNA REPAIR; INHIBITION; RADIOSENSITIZERS; DYNAMIC FUNCTION STUDIES; IMMUNOSUPPRESSIVE DRUGS; RADIOSENSITIVITY EFFECTS; LOW DOSE IRRADIATION; NAD; STRAND BREAKS; THYMOCYTES; GAMMA RADIATION; RATS; BIOLOGICAL RADIATION EFFECTS

Citation Formats

Smit, J A, and Stark, J H. Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes. United States: N. p., 1994. Web. doi:10.2307/3578794.
Smit, J A, & Stark, J H. Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes. United States. https://doi.org/10.2307/3578794
Smit, J A, and Stark, J H. Sat . "Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes". United States. https://doi.org/10.2307/3578794.
@article{osti_45269,
title = {Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes},
author = {Smit, J A and Stark, J H},
abstractNote = {This study assessed the ability of 11 established and potential radiosensitizing agents to retard the repair of radiation-induced DNA damage with a view to enhancing the immunosuppressive effects of in vivo lymphoid irradiation. The capability of irradiated rat thymocytes to repair DNA damage was assessed by an adaptation of the fluorimetric unwinding method. Three compounds, 3-aminobenzamide (3-AB), novobiocin and flavone-8-acetic acid (FAA), inhibited repair significantly. We also report the effect of low-dose irradiation combined with repair inhibitors on the relationship between DNA strand breaks, fragmentation, cell viability and use of nicotinamide adenine dinucleotide (NAD). DNA fragmentation was increased by 1 mM/l FAA, 1 mM/l novobiocin and 50 {mu}M/l RS-61443 within 3 h of incubation. The latter two compounds also proved cytotoxic. All three drugs augmented the effect of ionizing radiation on the use of NAD. Of the agents investigated, FAA showed the most promise for augmenting the immunosuppressive action of irradiation at nontoxic, pharmacokinetically achievable concentrations. 33 refs., 1 fig., 2 tabs.},
doi = {10.2307/3578794},
url = {https://www.osti.gov/biblio/45269}, journal = {Radiation Research},
number = 1,
volume = 137,
place = {United States},
year = {1994},
month = {1}
}