RADIOBIOLOGICAL STUDIES OF PC-3 AND DU-145 HUMAN PROSTATE-CANCER CELLS - X-RAY-SENSITIVITY INVITRO AND HYPOXIC FRACTIONS OF XENOGRAFTED TUMORS INVIVO

Purpose: To determine the quantitative responses to x-irradiation of exponentially growing human prostatic cancer cell lines PC-3 and DU-145 in vitro, and to determine the hypoxic percentages of these two cell lines when grown in vivo as xenografted solid tumors in nude mice. Methods and Materials: Radiation survival in vitro was quantitated using both single-hit, multitarget and linear-quadratic formalisms. Hypoxic fractions in vivo were determined from tumors of average sizes of about 750 mm3 using clonogenic excision assay. Results: In vitro, the average single-hit, multitarget survival values for 7 replicate experiments for the DU-145 line were n = 1.92 (1.39-2.65), D(q)(Gy) = 1.25, and D(o)(Gy) = 1.91 (1.88-1.94) (all values in parentheses indicate 95% confidence limits). For the PC-3 line (10 replicate experiments), these values were n = 2.84 (2.11-2.79), D(q)(Gy) = 1.02, and D(o)(Gy) = 1.06 (0.87-1.25). For the linear-quadratic formalism, values of alpha(Gy-1 X 10(1)) and beta(Gy-2 X 10(2)) for the DU-145 and PC-3 lines were, respectively, 1.55 (0.42) and 5.21 (1.09); and 4.87 (1.11) and 5.50 (1.88). The mean percentage survival of the DU-145 and PC-3 lines at a dose of 2 Gy were, respectively, 59.8 (533-67.0) and 32.0 (25.8-38.2). In vivo, the hypoxic fractions for the DU-145 and PC-3 tumors were, respectively, 7.20 (4.30-11.5), and 52.3 (42.8-63.9). Results: The data from the in vitro experiments show that the DU-145 cell line is significantly more radio-resistant than the PC-3 cell line. In vivo, the DU-145 tumors exhibit a significantly lower hypoxic percentage than do PC-3 neoplasms. Conclusions: Results indicate that significantly variability exists within human prostate tumors in regard to both intrinsic radiosensitivity in vitro and levels of hypoxia in vivo. Because these data appear to be the first published information on the intrinsic radiosensitivity and intratumor hypoxia characteristics of human prostate cancer, additional studies are needed to define the distributional aspects of these clinically relevant endpoints.