Proliferative activity of human tumors: assessment using bromodeoxyuridine and flow cytometry.

Cell kinetics of human carcinoma xenografts and human solid tumors were evaluated by means of two-color flow cytometry using single sampling at appropriate time intervals after bromodeoxyuridine (BrdU) labeling. The tumors were resected several hours after the administration of BrdU, and flow cytometry was used to measure the DNA content and BrdU incorporation. Once the BrdU labeling index (LI) and DNA synthesis time (Ts) were obtained, the potential doubling time (Tpot) was calculated from these values. In 11 xenografts, the cell kinetic data were compared with the actual tumor doubling time (Td), and a good correlation between Tpot and Td was obtained (r = 0.91, P less than 0.005). In a clinical study, 33 patients with gastric cancer, colorectal cancer, lung cancer, or other solid tumors were analyzed. Aneuploid tumors had a significantly higher LI value (P less than 0.01) and a shorter Tpot than diploid tumors. The cell loss rate of human tumors ranged from 40% to 80%. These cell kinetic parameters therefore accurately indicated the level of proliferative activity of human tumors.

bromodeoxyuridine

DNA index

labeling index

relative movement

DNA synthesis time

potential doubling time

tumor doubling time

fluorescence of S‐phase cells

fluorescence of G1, ‐phase cells

fluorescence of G2‐phase cells