Radioresistant cultures of the L5178Y leukemia were obtained during continuous β-irradiation at 4.8 rads/hour by means of tritiated water incorporated in the culture medium. The development of radiation resistance in individual cultures after exposures of 39 days or more (total dose ≥ 4.6 krads) was shown to be due to the production of resistant mutants during the course of irradiation. In the resistant cell strains derived from the mutants the chromosome count was unchanged from the modal value of 40, and the ability to grow in the DBA/2 mouse was unchanged. In the absence of radiation, resistant cultures grew rather more slowly than normal cells. Under continuous irradiation the mutants differed from each other in growth rate and in the proportion of dead cells present. The resistant cell strains were maintained at 4.8 rads/hour for nearly a year, during which the growth rate of the less resistant cultures speeded up in steps corresponding to the occurrence of further mutations, eventually reaching about the same growth rate as the initially more resistant cultures. The mutants initially obtained differed from each other in their response to acute irradiation with x-rays at 30 rads/min and on the basis of their dose response curve could be classified into two groups: those showing an increase in Dq (the dose at the point where the extrapolated exponential part of the curve intersects the abscissa corresponding to 100% survival) and a small increase in D0, and those showing no increase in Dq and a substantial increase in D0. The highest survival during continuous irradiation occurred in the group with an increased Dq; this shows that under continuous irradiation at the low dose rate used survival is determined by the properties of the cell reflected in the shoulder of the dose-response curve obtained from acute irradiation rather than the slope.

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