Evidence for indirect involvement of thymidine kinase in excision repair processes in mouse cell lines.
Wild-type cells and thymidine kinase-deficient clones from two mouse lymphoma cell lines, P388 and L5178Y, were compared for sensitivity to killing by the mutagens, ultraviolet irradiation (UV), ethyl methane sulfonate (EMS), and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Two out of three thymidine kinase-deficient P388 clones showed significantly enhanced sensitivity to killing by all three mutagens. This increased sensitivity to killing was also reflected in increased mutagenesis by the three mutagens. In the L5178Y cell line, wild-type cells showed little difference to two thymidine kinase-deficient clones in terms of mutagen sensitivity. This indicates that thymidine kinase may be significant for DNA repair processes in P388 but not in L5178Y cells. Unscheduled DNA synthesis (UDS) experiments were carried out on P388 and L5178Y wild-type cells and wild-type Friend leukemia cells (which are mutagen-sensitive when deficient in thymidine kinase). The UDS experiments showed the L5178Y cells were low in excision repair abilities relative to the P388 cells and the Friend cell clone. This indicates that the increased mutagen sensitivity in thymidine kinase-deficient P388 and clone 707 Friend cells may be due to thymidine kinase playing an indirect role in DNA excision repair, a process which is of little significance in the L5178Y cell line.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D004351:Drug Resistance; D007940:Leukemia L5178 / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D007941:Leukemia P388 / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D007942:Leukemia, Experimental / Q000235:genetics*; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D013866:Thioguanine / Q000494:pharmacology; D013937:Thymidine Kinase / Q000172:deficiency / Q000235:genetics*; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D009153:Mutagens; D013937:Thymidine Kinase; D013866:Thioguanine