RADIATION SENSITIVITY OF MERKEL CELL-CARCINOMA CELL-LINES

Purpose: Merkel cell carcinoma (MCC), being a small sell carcinoma, wo uld be expected to be sensitive to radiation, Clinical analysis of pat ients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Methods and Materials: Some of the MCC lines g rew as suspension cultures and could not be single cell cloned; theref ore, it was not possible to use clonogenic survival for all cell lines . A tetrazolium based (MTT) assay was used for these lines, to estimat e cell growth after gamma irradiation. Control experiments were conduc ted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC1 3, to demonstrate that the two assays were comparable under the condit ions used. Results: We have examined cell lines from MCC, small cell l ung cancer (SCLC), malignant melanomas, Epstein Parr virus (EBV) trans formed lymphocytes (LCL), and skin fibroblasts for their sensitivity t o gamma irradiation using both clonogenic cell survival and MTT assays . The results show that the tumor cell lines have a range of sensitivi ties, with melanoma being more resistant (surviving fraction at 2 Gy ( SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 rang e 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts we re the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay , when compared to clonogenic assay for the MCC13 adherent line and th e LCL, gave comparable results under the conditions used. Conclusion: Both assays gave a range of SF2 values for the MCC cell lines, suggest ing that these cancers would give a heterogeneous response in vivo. Th e results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.3 8, MCC14/2 0.45) would further suggest that some of them may develop r esistance during clonogenic evolution.