Studies of variation in inherent sensitivities to radiation, 5-fluorouracil and methotrexate in a series of human and murine tumor cell lines in vitro.
Clinical studies have reported reduced response rates to subsequent chemotherapy in certain tumors recurring after radiotherapy. We have investigated whether there are any correlations between radiation and drug responses in vitro using a range of murine and human tumor cell lines. We have compared sensitivities to X-irradiation and to 24 hr exposures to two widely used antitumor drugs, methotrexate and 5-fluorouracil. The 4 murine lines 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 values of 0.018-14.9 micrograms/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 microgram/ml and was unrelated to radiation response. In contrast, in the human lines tested, no correlations were observed between drug sensitivities and radiation response. The six lines tested (3 derived from epidermoid head and neck tumors, 2 from neuroblastomas and 1 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. Similarly, no correlations between response to 5-fluorouracil and radiation or 5-fluorouracil and methotrexate were noted, which is inconsistent with results using murine cells.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004361:Drug Tolerance; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D011836:Radiation Tolerance
D005472:Fluorouracil; D008727:Methotrexate