Human colonic tumor cell kinetics: potential for therapy

Using new in vitro techniques developed at the Cancer Research Unit, cell kinetic measurements were obtained in primary and metastatic human colonic tumors, polyps and normal bowel that did not require in vivo 3HTdR and required only single samples of tissue. These techniques included the measurement of the number of cells in DNA synthesis (LI), an estimate of the DNA synthesis time (Ts) and the growth fraction of tissues by means of the primer-available DNA-dependent DNA polymerase assay (PDP). From these data, the potential doubling time and the cell cycle time (Tc) of the tumors were calculated. Early preliminary data on human colonic specimens presented in Tables 1 and 2 indicate that there is an increase in LI from the low polyps to higher adenocarcinomas. There is little difference between primary and metastatic tumor cell kinetics. Growth fraction estimates (PDP) of the various colonic tissue types are also not significantly different and except for villous adenomas, DNA synthesis times are constant. The median 3HTdR labeling indices of 7% primary adenocarcinomas include a number of samples (approximately 20% of all samples) with high labeling indices (in the 10--20% range). These high labeling tumors may be those that show objective response to S-phase active drugs, e.g., 5-FU.