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Radiation Sensitivity of Cell Strains from Families with Genetic Disorders Predisposing to Radiation-induced Cancer¹

Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115 [J. B. L., H. N.]; Merck Research Institute, West Point, Pennsylvania 19486 [W. W. N., P. T.]; and The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030 [L. C. S.]

This investigation was designed to test the hypothesis that skin fibroblasts from patients with genetic disorders characterized by hypersusceptibility to X-ray-induced cancer are sensitive to the cytotoxic or clastogenic effects of X-irradiation in vitro. Cell strains were established from 28 specifically ascertained patients from families with nevoid basal cell carcinoma syndrome, retinoblastoma, or other disorders apparently predisposing to radiation-induced cancer. These included 10 patients with a clear personal or family history of radiation-induced tumors. These cell strains were examined for the cytotoxic effects of X-irradiation in 3 distinct series of separate, blinded experiments, along with a group of 9 similarly coded cell bank controls. Cells from 11 of these patients and 6 controls were studied for sensitivity to X-ray-induced chromosomal aberrations. Seven of the 37 cell strains were moderately hypersensitive to radiation-induced cell killing; 2 of these were from patients with radiation-induced tumors and 1 was a cell bank control. These results suggest that such isolated cases of hypersensitivity probably do not relate to the underlying genetic disorder. Overall, the X-ray response of cells from affected individuals in this study showed no systematic difference from that of cells from nonaffected relatives or cell bank controls for either cytotoxicity or clastogenicity.

¹ This work was supported by Grants CA-27925, CA-33624, CA-47542, and ES-00002 from the NIH.

² To whom requests for reprints should be addressed.

Received 1/26/89. Revised 5/ 8/89. Accepted 5/16/89.

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