Inhibiting the repair of DNA damage induced by gamma irradiation in rat thymocytes.
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/1 FAA, 1 mM/l novobiocin and 50 microM/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.
Smit
J A
JA
Department of Surgery, University of the Witwatersrand Medical School, Johannesburg, South Africa.
Stark
J H
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016590:Aphidicolin / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005720:Gamma Rays; D007700:Kinetics; D009285:Naphthoquinones / Q000494:pharmacology; D009675:Novobiocin / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors; D014740:Vidarabine / Q000494:pharmacology
D000970:Antineoplastic Agents; D001549:Benzamides; D005419:Flavonoids; D009285:Naphthoquinones; D011838:Radiation-Sensitizing Agents; D003561:Cytarabine; D009675:Novobiocin; D016590:Aphidicolin; C014638:beta-lapachone; D004317:Doxorubicin; C049328:flavone acetic acid; C025160:3-aminobenzamide; D014740:Vidarabine