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Local Control of T2/3 Transitional Cell Carcinoma of Bladder Is Correlated to Differences in DNA Supercoiling: Evidence for Two Discrete Tumor Populations¹

Department of Immunology, The Medical School, Birmingham University [A. T. M. V., P. A., R. P. B.], and Department of Urology, Queen Elizabeth Medical Center [D. M. A. W., T. H. L.], Birmingham B15 2TJ, United Kingdom

Single cell tumor suspensions were prepared from biopsy and urine samples from 48 patients with muscle invasive transitional cell carcinoma of the bladder. Prior to therapy, samples were irradiated in vitro with the condensation of DNA supercolls measured by the light scattered within a flow cytometer. Six months after completing a course of radiotherapy, the in vitro data were correlated with the presence or absence of local disease. After 12-Gy irradiation, nucleoid extraction and staining with 50 µg/ml ethidium bromide, 2 predominant forms of supercoiling behavior were seen. Nucleoids scattered either approximately 10% (Type I) or 35% (Type II) more light than unirradiated controls. Those patients with residual disease showed more Type I behavior (21 of 25; 84%) than those patients clear of disease (9 of 23; 39%) (P = 0.02). It is proposed that the ability of these tumor samples to adopt positive supercoiling after irradiation is related to a stronger association between individual DNA loops and their attachment to the nuclear matrix. This difference in nucleoid response within these tumor samples may be related both to intrinsic cellular radiosensitivity and, subsequently, to clinical radiocurability.

¹ We wish to acknowledge the support of the Cancer Research Campaign, United Kingdom (SP 1912), and the American Cancer Society for the funding necessary to carry out this study.

² To whom requests for reprints should be addressed, at Department of Radiotherapy, Loyola University Medical School, Maywood, IL 60141.

Received 10/22/92. Accepted 3/11/93.