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In Vitro X-Ray Sensitivity in Ataxia Telangiectasia Homozygote and Heterozygote Skin Fibroblasts under Oxic and Hypoxic Conditions

Radiation Oncology Branch, Division of Cancer Treatment, National Cancer Institute [T. J. K., J. B. M., S. M., A. R.] and National Institute of Arthritis and Metabolic Diseases [F. T.] NIH, Bethesda, Maryland 20205

Heterozygotes for ataxia telangiectasia (AT) are reported to have an increased risk of cancer especially prior to age 45 years. Cultured skin fibroblasts from some AT heterozygotes are reported to show increased sensitivity to the lethal effects of X-irradiation under hypoxia which is intermediate between the response of AT homozygote and normal control fibroblasts. This in vitro colony formation assay has been suggested as a clinical screen for presumed AT heterozygotes (relatives of AT homozygotes) to identify individuals at high risk for cancer. It has also been speculated that this radiosensitivity under hypoxia may represent a previously unrecognized DNA repair defect.

We have studied the response to X-irradiation of cultured skin fibroblasts from three AT families and two normal controls to further explore these observations. In contrast to the previous report, we did not find any difference in radiation survival (D_O) of fibroblasts from obligate AT heterozygotes in these families compared to normal control fibroblasts. We report normal oxygen enhancement ratios comparing radiosensitivity (D_O) under hypoxia to air for the fibroblast cultures of AT homozygotes, heterozygotes, and normal controls. Additionally, we report no difference in glutathione content of log-phase cells in AT heterozygotes and normal control fibroblasts.

We conclude that the radiation survival in air and hypoxia of AT heterozygote skin fibroblasts is similar to that of normal control cell lines. Low plating efficiency, variable extrapolation numbers in air and hypoxia, and cell density effects in some cell lines make it difficult to determine a meaningful oxygen enhancement ratio for these cells. We do not find the response to X-irradiation under hypoxia to be a useful in vitro marker for AT heterozygotes.

¹ To whom requests for reprints should be addressed.

Received 4/20/82. Accepted 6/29/82.