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Kinetics of Transitional Tumor Cell Line 4909 Adherence to Injured Urothelial Surfaces in F-344 Rats¹

Department of Urology, University of Iowa School of Medicine, Iowa City, Iowa 52240 [W. A. S., R. D. W.], and Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195 [P. H. C.]

Prior reports have described the mechanism initially responsible for transitional tumor cell adherence and implantation on injured urothelial surfaces. This study further quantifies variables that influence the size of tumor inoculum at the injury site and thereby affect bladder tumor recurrence risk. The surface area of urothelial injury, the concentration of tumor cells in the intravesical bathing medium, the viability of tumor cells, the time of urothelial exposure to tumor cells, and the intravesical pressure were the variables studied. Increasing the surface area of urothelial injury resulted in a linear increase in the size of the tumor inoculum (r² = 0.805, P = 0.0001). Tumor inoculum increased as a direct function of the concentration of tumor cells in the bathing medium. This relationship was linear at low cell concentrations (r² = 0.64, P = 0.0001). Higher concentrations of tumor cells appeared to result in saturation of the system, with a relationship best described by a log/log function (r² = 0.975, P = 0.0001). Viable and nonviable tumor cells appeared to compete for available binding sites with equal efficacy. A simple logarithmic relationship was seen for the effect of exposure time on the size of the tumor inoculum (r² = 0.513, P = 0.0198). Tumor inoculum increased as a linear function of the intravesical pressure (r² = 0.314, P = 0.0125). These results demonstrate a significant positive correlation between each of the experimental variables and the size of tumor inoculum. Manipulation of these variables in clinical practice may alter the size of tumor inoculum and thereby have an impact on tumor recurrence secondary to implantation.

¹ This work was supported in part by the Iowa City Veterans Affairs Medical Center and a grant from the American Foundation for Urologic Disease.

² Current address: Department of Urology, University of Iowa Hospital, Iowa City, Iowa 52242. To whom requests for reprints should be addressed.

Received 8/31/89. Revised 12/27/89.