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Altered p53 Status Correlates with Differences in Sensitivity to Radiation-induced Mutation and Apoptosis in Two Closely Related Human Lymphoblast Lines¹

Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115 [F. X., X. W., N-M. T., K. T. K., H. L. L.]; Department of Medicine, Renal Division, Boston University School of Medicine, Boston, Massachusetts 02118 [Y-H. W.]; and Department of Pathology, University of Vermont, Burlington, Vermont 05405 [D. W. Y.]

Previous work identified TK6 and WTK1 as human lymphoblast cell lines from one donor that have different capacities to catalyze recombination and that vary significantly in their response to ionizing radiation. WTK1 cells are more resistant to the toxic effects of X-rays yet more sensitive to induced mutation. We demonstrate here that although both cell lines contain equal levels of p53 mRNA, baseline protein levels are 4 times higher in WTK1. Irradiation leads to higher levels of p53 protein in both lines but to a greater extent in TK6. TK6 contains a wild-type p53 sequence, while WTK1 has a homozygous mutation in codon 237 of exon 7. We also observed a significant difference in the kinetics but not the overall degree of apoptosis induced by X-rays in these cells; apoptotic death is delayed for 3 days in WTK1. We hypothesize that this p53 mutation is responsible for the difference in apoptosis as well as for the differences in mutability and mutational spectra reported previously.

¹ This work was supported by American Cancer Society Grant CN-68A.

² To whom requests for reprints should be addressed, at Harvard School of Public Health, Department of Cancer Biology, 665 Huntington Avenue, 1-209, Boston, MA 02115.

Received 10/25/94. Accepted 11/15/94.

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