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Intrinsic Radiosensitivity of Normal Human Fibroblasts and Lymphocytes after High- and Low-Dose-Rate Irradiation¹

Departments of Experimental Radiotherapy [F. B. G., J. L. W., S. S. S., W. A. B.], Clinical Radiotherapy [F. B. G., L. J. P., K. K. A.], Head and Neck Surgery [D. L. C.], and Biomathematics [R. G.], The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, and Laboratoire de Radiobiologie Cellulaire, Unité INSERM 247, Institut Gustave Roussy, 94805 Villejuif, France [E. P. M.]

The existence of heritable radiosensitivity syndromes and clinical observations in radiotherapy patients suggests that human cellular radiosensitivity differs among individuals. We report here an in vitro study of radiosensitivity in 30 fibroblast and 29 lymphocyte cultures obtained from cancer patients and controls. In 25 cases, both fibroblasts and lymphocytes were obtained from the same donors. Fibroblasts were cultured from skin biopsy samples, and peripheral T-cell lymphocytes were cultured from blood. Clonogenic survival assays were performed by using high- and low-dose-rate irradiation; lymphocytes were in G_o phase and fibroblasts in confluent plateau phase. Various end points were calculated and compared (i.e., surviving fraction at 2 Gy, initial slope of the survival curve, and doses resulting in 10 and 1% survival, respectively). Depending on the end point, the coefficient of variation of the survival parameters ranged from 31 to 68% for lymphocytes and 21 to 41% for fibroblasts following high-dose-rate irradiation. Similar ranges were obtained after low-dose-rate irradiation. Variance analysis performed on replicate assays in cultures derived from the same patient showed that variation due to technical or sampling errors was significantly lower than variation between individuals (P = 0.00034 and 0.014 for fibroblasts and lymphocytes, respectively). No correlation was observed between the radiosensitivity of lymphocyte and fibroblast cultures derived from the same donors. We conclude that there is significant variation in normal cell radiosensitivity among individuals. On the other hand, comparisons of lymphocyte and fibroblast radiosensitivities suggest that tissue-specific characteristics, such as differentiation status, may variably modulate radiosensitivity.

¹ This investigation was supported by research grants from the National Cancer Institute (CA-50192, CA-06294, and CA-16672), the Association pour la Recherche sur le Cancer, the University Cancer Foundation, and the Katharine M. Unsworth Charitable Annuity Lead Trust.

² To whom requests for reprints should be addressed, at Department of Radiotherapy, Box 97, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.

Received 6/18/92. Accepted 9/ 3/92.

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