Differential antimutagenicity of WR-1065 added after irradiation in L5178Y cell lines.
The purpose of this study was to determine the antimutagenicity of WR-1065 added after irradiation of cells of cell lines differing in their ability to rejoin radiation-induced DNA double-strand breaks (DSBs). The postirradiation antimutagenicity of WR-1065 at the thymidine kinase locus was demonstrated for L5178Y (LY)-S1 cells that are deficient in repair of DNA DSBs. Less postirradiation antimutagenicity of WR-1065 was observed in LY-R16 and LY-SR1 cells, which are relatively efficient in DSB repair. Postirradiation treatment with WR-1065 had only a small stimulatory effect on DSB rejoining. A 3-h incubation of irradiated LY cells with WR-1065 caused slight changes in the distribution of cells in the phases of the cell cycle that differed between LY-S1 and LY-SR1 cells. Both LY-S1 and LY-SR1 cells were protected against the cytotoxic and mutagenic effects of radiation when WR-1065 was present 30 min before and during the irradiation. We conclude that the differential postirradiation effects of WR-1065 in the LY-S1 and LY-SR1 cells are not caused by differences in cellular uptake of the radioprotector or in its radical scavenging activity. Possible mechanisms for the postirradiation antimutagenicity of WR-1065 are discussed.
Evans
H H
HH
Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4942, USA.
Horng
M F
MF
Ricanati
M
M
McCoy
E C
EC
D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects; D007940:Leukemia L5178 / Q000235:genetics*; D008624:Mercaptoethylamines / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D013937:Thymidine Kinase / Q000235:genetics; D014407:Tumor Cells, Cultured
D016587:Antimutagenic Agents; D008624:Mercaptoethylamines; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004247:DNA; D013937:Thymidine Kinase