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Different sensitivity to cell killing and chromosome mutation induction by gamma rays in two human lymphoblastoid cell lines derived from a single donor: possible role of apoptosis.

The gamma-ray sensitivity of two human lymphoblastoid cell lines, TK6 and WI-L2-NS, was studied; both cell lines are derived from the same parent, WI-L2. TK6 was more sensitive to the cytotoxic effects of gamma rays, but showed fewer induced chromosome aberrations. There was no difference between the two cell lines in their capacity to rejoin DNA double-strand breaks or in the kinetics of the rejoining process. The kinetics of cell cycle progression following radiation exposure was also similar in TK6 and WI-L2-NS. However, while TK6 cells were very sensitive to apoptosis induction, showing high levels of apoptotic cells within 24 h of exposure, no evidence for any significant levels of apoptosis was found for WI-L2-NS within 30 h of irradiation, when chromosome aberration frequency was determined. Evidence of apotosis were seen at later times in WI-L2-NS cells, but the levels were significantly lower than comparably treated TK6 cells. The results support a hypothesis that the lower survival and induced aberration frequencies in TK6 cells are due to selective removal of damaged cells by apoptotic processes prior to analysis of chromosome aberration frequencies in mitosis.