Mutation of xeroderma pigmentosum lymphoblasts by far-ultraviolet light.
Survival and mutation were measured after UV irradiation in a human diploid B-lymphoblastoid line, XPA3, derived from a xeroderma pigmentosum patient of complementation group C. Relative to a normal human lymphoblastoid line, the XPA3 cells were more sensitive to killing as evidenced by a diminished shoulder in the survival curve and a steeper slope in the log-linear portion of the survival curve. While XPA3 cells were also more sensitive to mutation than normal cells, the data are complex. We interpret them to show a diminished threshold and a greater slope in the mutation curve at fluences which are not appreciably toxic. Examination of the 3H-TdR labeling index and rate of DNA synthesis after irradiation indicated that, at low equitoxic UV fluences (S greater than or equal to 0.85), XPA3 cells in S phase failed to slow their rate of DNA synthesis to the same extent as normal cells. Thus, fewer XPA3 than normal cells accumulated in S phase at relatively non-toxic fluences. However, at fluences which were toxic to XPA3 but not to normal cells, the early effects on DNA synthesis for both cell types were virtually indistinguishable. Our observations suggest that XPA3 cells have a reduced repair capacity for UV damage both because of a reduced rate of DNA repair and because uninterrupted passage through S phase reduced the time available for repair before fixation of both lethal and mutational damage. Furthermore, we interpret the relatively greater slopes in survival and mutation curves as an indication that, in XPA3 cells, there is a greater probability that an unrepaired lesion will result in cell death or mutation.
D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D004260:DNA Repair; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D009154:Mutation / Q000528:radiation effects*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*