STUDIES OF VARIATION IN INHERENT SENSITIVITIES TO RADIATION, 5-FLUOROURACIL AND METHOTREXATE IN A SERIES OF HUMAN AND MURINE TUMOR-CELL LINES INVITRO

Clinical studies have reported reduced response rates to subsequent chemotherapy in certain tumors recurring after radiotherapy. Whether there are any correlations between radiation and drug responses was investigated in vitro using a range of murine and human tumor cell lines. Sensitivities to X-irradiation and to 24 h exposures to 2 widely used antitumor drugs, methotrexate and 5-fluorouracil, were compared. The 4 murine lines [lymphoma L1578Y cells] selected showed a range of radiation responses with Do values of 0.48-0.76 Gy. Methotrexate sensitivities also exhibited an 800-fold difference (IC50 [median inhibitory concentration] values of 0.018-14.9 .mu.g/ml) which appeared to correlate inversely with radiation response. Sensitivity to 5-FU was less variable in these cells with a range of IC50 values of 0.056-0.43 .mu.g/ml, and was unrelated to radiation response. In the human lines tested, no correlations were observed between drug sensitivities and radiation response. The 6 lines tested ([HN-1, TR-126 and HEP-2 cells] derived from epidermoid head and neck tumors, [CHP-100 and LAN-1 cells] from neuroblastomas and [LOVO cells] from a colon carcinoma) showed a range of radiation responses with Do values of 0.66-1.59 Gy. Methotrexate sensitivities ranged only over a 150-fold concentration but, contrasting with data from the murine cells, no correlation with radiation response was apparent. No correlations between response to 5-fluorouracil and radiation or 5-fluorouracil and methotrexate were noted, which is inconsistent with results using murine cells.