LOCAL-CONTROL OF T2 3 TRANSITIONAL CELL-CARCINOMA OF BLADDER IS CORRELATED TO DIFFERENCES IN DNA SUPERCOILING - EVIDENCE FOR 2 DISCRETE TUMOR POPULATIONS/

Single cell tumor suspensions were PrePared from biopsy and urine samp les from 48 patients with muscle invasive transitional cell carcinoma of the bladder. Prior to therapy, samples were irradiated in vitro wit h the condensation of DNA supercoils measured by the light scattered w ithin a flow cytometer. Six months after completing a course of radiot herapy, the in vitro data were correlated with the presence or absence of local disease. After 12-Gy irradiation, nucleoid extraction and st aining with 50 mug/ml ethidium bromide, 2 predominant forms of superco iling behavior were seen. Nucleoids scattered either approximately 10% (Type I) or 35% (Type II) more light than unirradiated controls. Thos e 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 posit ive supercoiling after irradiation is related to a stronger associatio n between individual DNA loops and their attachment to the nuclear mat rix. This difference in nucleoid response within these tumor samples m ay be related both to intrinsic cellular radiosensitivity and, subsequ ently, to clinical radiocurability.