Cell population kinetics of 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse

Abstract

Summary The parameters of cell population kinetics of symmetrical 1,2-dimethylhydrazine-induced colonic neoplasms and their adjacent colonic mucosa in the mouse were analyzed using the fraction labeled-mitoses curve method and compared with those of three groups of epithelial cells in the crypt of the descending colon of normal mouse. The analysis of three groups of epithelial cells in the crypt of normal mouse indicates that differentiation of epithelial cells was associated not only with a smaller proliferative pool of cells but also with a shortening of the duration of G₂ phase and a prolongation of mitotic time. Other parameters of cell cycle did not change significantly. The mean cell cycle time of neoplastic cells in chemically induced colonic neoplasms was similar to that of epithelial cells in normal colon, but the variance was much greater in neoplastic cells. In neoplastic cells, the proliferative pool was greater, the G₁ phase prolonged, and the S phase and the mitotic time became shorter as compared to epithelial cells in normal colon. The duration of G₂ phase of neoplastic cells fell between the values of presumptive stem cells and differentiating cells in normal colon, compatible with the hypothesis that neoplastic cells are transformed stem cells defective in cellular differentiation. In the colonic mucosa immediately adjacent to neoplasms, the fractionlabeled-mitoses curve showed a flat second wave, indicating that the group of cells initially labeled by the pulse became a mixture of cells, some continuing the proliferative cycle normally, some going out of cycle, some slowing down in their passage from S through G₂ to M, and some being arrested in mitotic phase. Such heterogeneous behavior of cells may be closely related to expansion of neoplasms. With some assumptions, however, cell cycle parameters of those normally cycling cells were estimated: the cell cycle time and the duration of G₁ phase and mitotic phase were prolonged as compared to neoplastic cells and epithelial cells of normal colon.