Production of Radioresistant Mutants in Murine L5178Y Lymphoma Cells

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Abstract
Radiation-resistant mutants of murine L5178Y lymphoma with stable phenotypes were produced with protracted X-irradiation. When a total dose equal to the LD50 of the acute dose-response curve is delivered per interdivision time, a condition approaching zero growth can be achieved. Because any resistant mutant created by the radiation will have a higher growth rate than the parental strain under irradiation, it will grow out of this equilibrium condition. Extrapolation of the final growth curve back to 1 cell with then yield the time at which such a mutation had occurred. For N live cells with a doubling time Td exposed to a dose rate R resulting in a total dose of TR delivered up to the time T of the appearance of the mutant, the probability (P) of producing such a mutant can be assessed as 1.6/NRT, assuming that the probability of producing such a particular mutation during any one cell generation is independent of the past history of the cell. Using this concept, the probability of producing a mutation under continuous irradiation (122 rad/day) and under continuously pulsed irradiation (107 rad, 6 pulses/day) was approximately 5 .times. 10-8/cell per rad. A similar probability was calculated using previously published data where tritiated water in the growth medium was used as the source for the continuous irradiation.

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