Effects of thymidine kinase and methyltransferase deficiency on mutagenesis in a human lymphoblastoid cell line.
In this study the effect of thymidine kinase (TK) deficiency on mutagen sensitivity was examined in the human lymphoblastoid cell line Raji. Wild-type and TK-deficient Raji cells were treated with a range of concentrations of ethyl methanesulphonate (EMS) and a range of doses of ultraviolet (UV) light, then examined for mutagen sensitivity as measured by cell survival and mutation to HGPRT deficiency. Dose-dependent responses were observed and TK-deficient cells exhibited decreased survivals and increased mutant frequencies relative to wild-type cells. TK-deficient Raji cells are also deficient in O6-methylguanine-DNA-methyltransferase. This may partially account for their sensitivity to EMS but does not account for the results obtained with UV. It is therefore likely that an additional factor, such as alterations in supply of deoxyribonucleoside triphosphates, may affect the mutagen sensitivity of Raji cells.
Best
C J
CJ
Department of Biological and Biomedical Sciences, University of Ulster at Coleraine, N. Ireland, UK.
McKelvey-Martin
V J
VJ
McKenna
P G
PG
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005020:Ethyl Methanesulfonate / Q000633:toxicity*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D016296:Mutagenesis; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D005020:Ethyl Methanesulfonate; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase; D013937:Thymidine Kinase