Cell proliferation of human leukemia and solid tumors studied with in vivo bromodeoxyuridine and flow cytometry

Abstract

Bromodeoxyuridine (BUDR) is a thymidine analog that is incorporated into the DNA of proliferating cells. Because the dose of BUDR that is needed to label cells is not toxic, cell labeling can be accomplished in vivo by infusing the substance into patients. A monoclonal antibody against BUDR is then used to identify BUDR-labeled cells. The same cell population can also be stained for DNA content with propidium iodide (PI). Using bivariate flow cytometry (FCM) for measurements, both the percentage of BUDR-labeled cells and their total DNA content can be evaluated. This technique allows one to obtain the labeling index (LI) and the DNA synthesis time (TS). The potential doubling time (Tpot) and the fractional turnover rate (FTR) can be mathematically derived. During a 15-month period, in vivo BUDR infusion to study cell kinetics was used in 112 consecutive patients with various types of malignant tumors: acute leukemia (50), gastric cancer (42), and brain gliomas (20). The procedure took 6 to 9 h to complete and there was no immediate toxicity from BUDR administration. Successful LI and TS determinations were obtained in 89 (80%) and in 80 (72%) of the 112 patients, respectively. Proliferative activity in 34 patients with acute nonlymphoblastic leukemias who were uniformly treated for remission induction and maintenance was measured from Tpot and FTR. It was greater in responsive than in nonresponsive patients, and in those who experienced remission for over 8 months than in those who had a shorter remission. Proliferative activity was also greater in patients with advanced gastric cancers than in those with more limited disease.(ABSTRACT TRUNCATED AT 250 WORDS)