Cell proliferation in human melanoma.
The cytokinetics of subcutaneous metastases in five patients with melanoma was studied. Multiple simultaneous biopsies following pulse labeling with tritiated thymidine were performed in one patient. There was relatively uniform labeling and mitotic indices among these. Within the individual tumors, there was some variation in the labeling index with small clusters of tumor cells having significantly higher labeling indices than more sparsely infiltrating tumor cells. Repetitive biopsies following pulse labeling were performed in two patients. The per cent labeled mitosis curves were similar in the two patients. By computer analysis a median G(2) period of 5.3 hr and an S period of 21 hr were obtained. The generation time (T(e)) was highly variable with a median of 3 days. This T(e) was consistent with that calculated from grain count studies in these patients. Two patients received either intermittent or continuous tritiated thymidine over a 10-20 day period. Analysis of the labeling index curve by computer fitting indicated a growth fraction of 20-30%. The growth fraction calculated by other indirect methods was consistent with the computer analysis. The potential tumor doubling time as calculated from the T(e) and growth fraction was much shorter than the actual doubling time indicating that cell loss was approximately 70% of the rate of cell production.