DNA cell cycle studies in uveal melanoma.

We analyzed the cell cycling status of a group of irradiated and nonirradiated uveal melanomas using BrdUrd techniques. These data demonstrate that melanomas are relatively slow-growing tumors with a few cells actively cycling at a given time. Radiation has a profound effect on the number of cycling cells (P less than .0001). After treatment with either 20 Gy of pre-enucleation photon or 60 Gy or more of helium ion irradiation, virtually no cells are detected in the synthesis phase of the DNA cell cycle. It is unclear whether the absence of cycling cells after 20 Gy of photon irradiation is permanent or represents a transient cell cycle block, since these tumors were studied within 48 hours after irradiation. In contrast, all melanomas treated with helium ion had been irradiated several months prior to enucleation (mean, 2 years). In the latter group of tumors, the length of time between treatment and cell cycle analysis suggests that these cells had lost their reproductive integrity. These data were substantiated by tissue culture studies. Growth of tumor explants was significantly less (P less than .007) in irradiated than in nonirradiated melanomas. The optimum technology used for measurement of cell cycle status remains to be determined. Measurement of BrdUrd uptake using immunofluorescent microscopy on either standard sections or fine-needle biopsies can be performed. In general, flow cytometric analysis yields similar results. It is difficult with the latter technique to be certain that nontumor cells are not artifactitiously counted in the cell cycle studies. The incorporation of BrdUrd cell cycle analysis with fine-needle biopsy may be useful in the clinical management of irradiated melanomas that have questionable growth after treatment. In a few cases studied, results appeared to correlate with tumor growth activity.