Loss of Tumorigenicity with Simultaneous Changes in Radiosensitivity and Photosensitivity during in Vitro Growth of L5178Y Murine Lymphoma Cells1

Murine leukemic lymphoblasts L5178Y-R (LY-R) undergo con version into their L5178Y-S (LY-S) variant as a result of pro longed (5 months to 4 years) cultivation in vitro. LY-R cells are highly tumorigenic in DBA/2 mice; resistant to X-rays [D0 (mean lethal dose [reciprocal of the slope of the linear portion of dosesurvival curve]) = 0.91 grays]; and sensitive to ultraviolet radia tion (D0 = 0.7 J/sq m), short (up to 60 min) heat (43°)treatment, and certain potential cancer drugs. LY-S cells are practically nontumorigenic in DBA/2 mice; sensitive to X-rays (D0 = 0.56 grays); and resistant to ultraviolet radiation (D0 = 5.5 J/sq m), short heat treatment, and the drugs. The differences in sensitivity of these two cell strains to physical and chemical agents are paralleled by differences in DMA repair efficiency. Although both strains can be cloned in soft agar, LY-S cells invariably show higher plating efficiencies. In vitro mean doubling times are 12 to 15 hr and ~10 hr for LY-R and LY-S cells, respectively. The actual loss of tumorigenicity and changes in radioand photosensitivity associated with conversion of LY-R cells into LY-S cells occur within a short time. This indicates that these changes (and probably other phenotypic changes mentioned above) result from a single event or from several events occurring within a relatively short time elicited by in vitro culture conditions.