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Effect of Preirradiation of Transplantation Site on Growth Characteristics and Hypoxic Fractions in Human Colon Tumor Xenografts¹

Department of Radiation Medicine and Radiation Research Laboratories, Brown University School of Medicine, Providence, Rhode Island 02912 [J. T. L., G. P., L. Q.], and Syntex Corporation, Institute for Research Data Management, Palo Alto, California 04303 [S. M.]

The volumetric growth curves and hypoxic fractions of seven different human colon tumor lines (clone A, clone D, WiDR, SW480, SW620, DLD-2, and HCT-8) xenografted into the flank regions of either unirradiated nude mice or mice that had received 17.5 Gy of 250-kVp X-rays 1 day prior to implantation were biomathematically analyzed using the Verhulstian equation. Significant variation was found among tumors with respect to both initial growth rates (r, days^-1) and theoretical final volumes (carrying capacities, K, mm³). In radiation-damaged normal tissue, tumors grew relatively well for about the first 2 wk postimplantation, attaining volumes of about 70 to 155 mm³. Then, tumor growth rates altered. This effect varied from relatively minor effects on growth rate (tumors of clones A and D) to inhibition of growth, with actual decreases in tumor volume (e.g., WiDr, SW480, SW620, HCT-8, and DLD-2). After this short-term transience in growth kinetics, neoplasms began to steadily regrow at about 3 wk postimplantation, albeit at a slower rate than that seen in controls. Tumor bed effect values were calculated using the ratio of times at which control tumors and tumors growing in the radiation-injured tissue reached a volume of 7.5% of the K values derived from the respective control growth curves. Values for clone D, clone A, and WiDR, SW480, SW620, DLD-2, and HCT-8 tumors were, respectively, 1.89, 2.41, 3.48, 3.62, 2.82, 3.66, and 3.65, indicating that tumor bed effect responses varied by almost 100%, even for cancers of the same neoplastic class. Also, the hypoxic fractions of all tumors growing in radiation-damaged sites were increased as compared with levels in controls.

¹ Research supported by a grant from the National Cancer Institute (CA 50350).

² To whom requests for reprints should be addressed, at Brown University School of Medicine, Radiation Research Laboratories, Box G, Room B-003, Providence, RI 02912.

Received 12/ 3/91. Accepted 2/ 4/92.

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