Identification and kinetics of G1 phase-confined cells in experimental mammary carcinomas

Three lines of mouse mammary carcinoma growing in isogenic hosts and differing in degree of histological differentiation and rates of proliferation were used to study parenchymal cells with various types of nucleoli. The relative number of cells possessing trabeculate or ring-shaped nucleoli or nucleolar fragments was closely related to the growth rate and degree of differentiation of tumor lines tested. All three subpopulations increased with increasing age and with decelerated tumor growth. In some cells in late telophase, either trabeculate or ring-shaped nucleoli could be distinguished in mitotic poles. This demonstrated that cells with these nucleoli are detected at the beginning of G1 phase. Even low levels of DNA synthesis, which would indicate that some cells with trabeculate or ring-shaped nucleoli or possessing nucleolar fragments were in S phase, could not be demonstrated. Microfluorometric measurements have indicated that cells with trabeculate and ring-shaped nucleoli have a DNA content close to 2c, whereas cells with dense nucleoli have a DNA content corresponding to either 2c, 2 to 4c, 4c, or greater than 4c. On the basis of these observations, it is concluded that cells with trabeculate and ring-shaped nucleoli and cells with nucleolar fragments either proceed slowly through G1 or are arrested in this phase. Cells with trabeculate nucleoli were replaced steadily, having a transit time of no longer than 84 hr. These cells constituted a "fast" component of cell renewal of G1-confined cells. A "slow" component, cells bearing ring-shaped nucleoli or nucleolar fragments, were replaced after a lag of 24 to 48 hr. with residency time for some of these cells being in excess of 84 hr.