Radiation and Melanoma: Response of B16 Mouse Tumor Cells and Clonal Lines to in Vitro Irradiation

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Abstract
B16 mouse melanoma cells taken directly from tumors could be plated at high plating efficiency in vitro. Carefully controlled determinations of the extrapolation number (n) and the mean lethal dose (Do) reveal an n of 2-4 and a Do of 163-193 rad (.alpha. ranges from 1.7-3.1 .times. 10-3 and .beta. from 1.2-2.4 .times. 10-6).Cells from young s.c. tumors tend to have higher values of n and lower values of Do than cells taken from advanced tumors. I.p. tumors of all ages exhibit a response similar to that of young s.c. tumors. When low numbers of viable cells are plated, the plating efficiency is improved by the presence of heavily irradiated feeder-layer cells. Tumor cells were irradiated both at constant cell number and at constant cell concentration. B16 tumor cells are capable of repairing sublethal damage. They are more sensitive when irradiated at 4.degree. C than at room temperature. Irradiation at dose rates higher than 113 rad per min does not affect the survival parameters. A high extrapolation number and a low Do are not obligatory features of melanoma cells. Ten clones were isolated from a B16 melanoma and irradiated at early passage. The values for n ranged from 1.7-4.6 with an average of 3.1, and for Do ranged from 146-260 rad with an average value of 195 rad (.alpha. ranged from 1.0 .times. 10-3-3.5 .times. 10-3 with a mean of 2.0 .times. 10-3, and .beta. ranged from 0.41 .times. 10-6-4.3 .times. 10-6 with a mean of 2.0 .times. 10-6). Seven clones were continued in culture for several more passages. Four showed changes in the radiation parameters. Both increases and decreases in n and Do were seen. One clone showed a 50% increase in Do on subculture. This same clone showed a 5- to 7-fold increase in n after in vivo passage with a concomitant decrease in Do. Return to in vitro passage brought about a decrease in n and an increase in Do. Cells in tumors apparently show considerable variation in their response to radiation; radiation parameters are not necessarily stable, but can undergo considerable evolution. Selection for more resistant cells in human melanomas could be a factor contributing to the general resistance of these tumors to radiation therapy.

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