Population Size and Radiosensitivity of Murine Hematopoietic Endogenous Long-Term Repopulating Cells

Abstract

Abstract A new assay is described that measures the numbers (n) of endogenous long-term repopulating cells (eLTRC) surviving sublethal irradiation. The assay is based on analysis of variances of Pgk-1a phenotypes within groups of sublethally irradiated Pgk-1a/b mice. When ln n is plotted as a function of dose, the radiosensitivity (D0) is the negative reciprocal of the slope and the y-intercept is N or total numbers of eLTRC per mouse. The assay is unique in that N is an absolute value not requiring correction for seeding efficiency, or f. From two independent estimates, total numbers of eLTRC were determined to be 8,700 or 11,900 cells per mouse and D0 was found to be 0.82 or 0.83 Gy. If eLTRC are, in fact, the long-term repopulating cells (LTRC) defined by classical transfer assay, then LTRC can home to the marrow with nearly unit efficiency, only one to two LTRC are required for a mouse to survive a radiation LD50/30, and LTRC possess nearly unlimited self-renewal potential.